subject:(Imaging Probes)

Columbia University

1. Fiala, Tomas. Polymer supported probes and drugs for targeted brain imaging and pharmacology.

Degree: 2020, Columbia University

URL: https://doi.org/10.7916/d8-dbv1-gp60

► This doctoral thesis details a series of projects at the border of chemistry and neuroscience leading to the development of a novel family of probes… (more)

▼ This doctoral thesis details a series of projects at the border of chemistry and neuroscience leading to the development of a novel family of probes which chemically target specific cells and molecules in the brain. Chapter 1 concisely introduces the history, development and applications of probes for monitoring brain activity and highlights synthetic voltage sensitive dyes as probes which have not yet reached their full potential, partly due to the lack of targeting strategies in brain tissue. Chapter 2 details the development of a new class of polymer-supported probes for ligand-directed delivery of fluorescent voltage sensitive dyes to monoaminergic neurons in live brain tissue. The polysaccharide dextran equipped with dichloropane as a ligand and either an electrochromic or PeT-based voltage sensor selectively targets dopaminergic and noradrenergic axons in mouse brain slice preparations. The new probes enabled voltage imaging in a defined neuronal population without the use of genetic manipulation. All following chapters describe modification of one of the components of the targeting platform developed in Chapter 2 aiming to optimize its performance or broaden its application potential. Chapter 3 extends the developed polymer platform to the targeting of a different molecular target – the AMPA-type glutamate receptor – via a ligand-directed covalent labeling strategy. Chapter 4 examines PEG as an alternative polymer carrier and shows that while dextran is more universal as a carrier, PEG provides superior targeting selectivity with negatively charged PeT-based voltage sensors. A series of targetable probes with improved voltage sensitivity based on the PEG platform is introduced here as well. Chapter 5 describes the synthesis of targetable probes carrying voltage sensors for imaging modalities other than visible light fluorescence, specifically for short wave infrared (SWIR) fluorescence and photoacoustic (PA) imaging. Chapter 6 shows the first steps towards adapting the delivery platform to the development of dual-ligand drugs for cell-selective pharmacology in the brain.

Subjects/Keywords: Chemistry; Brain – Imaging; Neurosciences – Research; Molecular probes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fiala, T. (2020). Polymer supported probes and drugs for targeted brain imaging and pharmacology. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/d8-dbv1-gp60

Chicago Manual of Style (16^th Edition):

Fiala, Tomas. “Polymer supported probes and drugs for targeted brain imaging and pharmacology.” 2020. Doctoral Dissertation, Columbia University. Accessed January 15, 2021. https://doi.org/10.7916/d8-dbv1-gp60.

MLA Handbook (7^th Edition):

Fiala, Tomas. “Polymer supported probes and drugs for targeted brain imaging and pharmacology.” 2020. Web. 15 Jan 2021.

Vancouver:

Fiala T. Polymer supported probes and drugs for targeted brain imaging and pharmacology. [Internet] [Doctoral dissertation]. Columbia University; 2020. [cited 2021 Jan 15]. Available from: https://doi.org/10.7916/d8-dbv1-gp60.

Council of Science Editors:

Fiala T. Polymer supported probes and drugs for targeted brain imaging and pharmacology. [Doctoral Dissertation]. Columbia University; 2020. Available from: https://doi.org/10.7916/d8-dbv1-gp60

University of Sydney

2. Shen, Clara. Fluorescent strategies to study the labile copper pool .

Degree: 2017, University of Sydney

URL: http://hdl.handle.net/2123/17594

► Copper plays a critical role in the structure and function of essential proteins. These proteins must draw copper from a labile and rapidly exchanging copper… (more)

▼ Copper plays a critical role in the structure and function of essential proteins. These proteins must draw copper from a labile and rapidly exchanging copper pool, which is able to change dynamically in response to cellular stresses or stimuli. When mismanaged, this pool can compromise the health and correct functioning of the cell. There is evidence that misregulation of the bioavailable copper pool is linked to neurodegenerative diseases and cancer, and recent studies have uncovered potential roles for copper as a signalling agent. This work has involved the strategic development of diverse sensing systems to image bioavailable copper in cells. First, the development of a ratiometric fluorescent copper sensor InCCu1 has enabled the selective imaging of mitochondrial copper pools. InCCu1 takes advantage of a dual fluorophore system, where one fluorophore is electronically conjugated to the receptor and therefore responsive to the concentration of copper, while the other provides a constant emission peak to internally standardise the probe's response. This probe was utilised in investigations of the relationship between cisplatin and copper homeostasis, as well as in multicellular organisms. The majority of fluorescent probes use fluorescence emission intensity or wavelength as the monitored parameter. Fluorescence lifetime offers another parameter that can be studied, but there are no reported lifetime-based Cu(I) probes. Here, CB-NS4, the first novel sensor for Cu(I) that exhibits changes in fluorescence lifetime, is reported. Interestingly, the probe displayed dual behaviour; its fluorescence lifetime was highly sensitive to the presence of Cu(I) but not Cu(II), while the reverse was observed in the emission parameter. Changes in copper levels in cells could be monitored using CB-NS4 by fluorescence lifetime imaging microscopy (FLIM). Finally, the development of reaction-based sensors for Cu(I) was explored. Reaction-based probes provide complementary information to previously reported probes, and may give insight about short-term fluctuations in metal concentration. To this end, ACCu1 was developed and its kinetics characterised. ACCu1 contains a trigger group masking a coumarin fluorophore, rendering it nearly non-fluorescent. Upon selective reaction with Cu(I), the trigger group is cleaved, releasing a highly fluorescent form of coumarin. While developing fluorescent sensors for species such as copper is challenging, this work demonstrates the utility of a number of distinct approaches, each of which can give rise to diverse probes with complementary properties and advantages. Importantly, this work has led to probes that respond in different parameters of detection, and novel sensors have been successfully applied to biological studies. This work highlights the importance of fluorescent sensors to enriching our understanding of the roles of copper in biology.

Subjects/Keywords: fluorescent probes; chemical biology; copper; cellular imaging

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APA (6^th Edition):

Shen, C. (2017). Fluorescent strategies to study the labile copper pool . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/17594

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shen, Clara. “Fluorescent strategies to study the labile copper pool .” 2017. Thesis, University of Sydney. Accessed January 15, 2021. http://hdl.handle.net/2123/17594.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shen, Clara. “Fluorescent strategies to study the labile copper pool .” 2017. Web. 15 Jan 2021.

Vancouver:

Shen C. Fluorescent strategies to study the labile copper pool . [Internet] [Thesis]. University of Sydney; 2017. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/2123/17594.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shen C. Fluorescent strategies to study the labile copper pool . [Thesis]. University of Sydney; 2017. Available from: http://hdl.handle.net/2123/17594

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Pesnel, Sabrina. Développement de modalités d'imagerie in vivo pour l'oncologie expérimentale. : Development of in vivo imaging modalities for experimental oncology.

Degree: Docteur es, Biologie cellulaire et moléculaire, 2010, Université d'Orléans

URL: http://www.theses.fr/2010ORLE2050

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L’imagerie in vivo du petit animal est de plus en plus utilisée en pharmacologie pour identifier et caractériser l’activité de nouveaux agents anticancéreux.La première partie… (more)

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L’imagerie in vivo du petit animal est de plus en plus utilisée en pharmacologie pour identifier et caractériser l’activité de nouveaux agents anticancéreux.La première partie de ma thèse a consisté à développer des outils pour améliorer la quantification enbioluminescence. Une méthode, basée sur les caractéristiques spectrales des photons émis, a été établie pour corriger l’absorption tissulaire. La seconde, faisant appel aux méthodes de restauration d’images, avait pour but de corriger la diffusion pour augmenter la résolution. Dans un second temps, j’ai mis en place des modèles in vivo de tumeurs expérimentales bioluminescentes (un glioblastome intracérébral, un lymphome anaplasique à grandes cellules et un neuroblastome métastatique) en utilisant les méthodes d’imagerie décrites précédemment. Ces études ont permis d’étendre la caractérisation de l’activité préclinique d’un nouvel agent anticancéreux. L’objectif de la dernière partie de mon travail était de développer des sondes d’imagerie. La première sonde, un anticorps monoclonal anti-CD45 marqué avec un fluorochrome a permis la détection de cellules leucémiques humaines implantées chez la souris en utilisant l’imagerie de fluorescence. La seconde a été développée pour prédire l’entrée d’un agent anticancéreux, un conjugué spermine-podophyllotoxin, dans les cellules tumorales via les transporteurs des polyamines. La sonde synthétisée est une spermine à laquelle un groupement HYNIC a été ajouté afin de pouvoir lier un radioisotope : le Technétium 99m et ainsi réaliser un examen scintigraphique. Les résultats ont démontré la faisabilité d’une application préclinique de cette sonde. Ainsi à l’issu de cette thèse, les méthodes de traitement des signaux de bioluminescence développées sont disponibles pour améliorer l’application de l’imagerie optique en pharmacologie. Bien sûr des études supplémentaires sont encore nécessaires pour définir précisément dans quel contexte ces corrections seront les plus appropriées.

Small animal imaging is more and more used in pharmacology to identify and to characterize the activities of new antitumor agents. The first part of my thesis consisted in the development of new tools to improve the quantitation in bioluminescence. A method, based on spectral characteristics of emitted photons, has been established to correct tissue absorption. The second, using methods of image restoration had for objective to correct tissue scattering to increase the resolution. In a second part, I developed in vivo models of bioluminescent tumors (intracranial glioblastoma, a large cell anaplastic lymphoma and a metastatic neuroblastoma) using the imaging methods described previously. These studies allowed the characterization of the activity of a new antitumor agent. The aim of the last part was to develop imaging probes. The first, a monoclonal antibody antiCD45 labeled with a fluorochrome allowed the detection of human leukemic cells implanted in the mice using fluorescence imaging. The second was developed to predict the uptake of a antitumor…

Advisors/Committee Members: Bailly, Christian (thesis director), Le Pape, Alain (thesis director).

Subjects/Keywords: Imagerie du petit animal; Sondes d’imagerie; Small animal imaging,; Imaging probes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pesnel, S. (2010). Développement de modalités d'imagerie in vivo pour l'oncologie expérimentale. : Development of in vivo imaging modalities for experimental oncology. (Doctoral Dissertation). Université d'Orléans. Retrieved from http://www.theses.fr/2010ORLE2050

Chicago Manual of Style (16^th Edition):

Pesnel, Sabrina. “Développement de modalités d'imagerie in vivo pour l'oncologie expérimentale. : Development of in vivo imaging modalities for experimental oncology.” 2010. Doctoral Dissertation, Université d'Orléans. Accessed January 15, 2021. http://www.theses.fr/2010ORLE2050.

MLA Handbook (7^th Edition):

Pesnel, Sabrina. “Développement de modalités d'imagerie in vivo pour l'oncologie expérimentale. : Development of in vivo imaging modalities for experimental oncology.” 2010. Web. 15 Jan 2021.

Vancouver:

Pesnel S. Développement de modalités d'imagerie in vivo pour l'oncologie expérimentale. : Development of in vivo imaging modalities for experimental oncology. [Internet] [Doctoral dissertation]. Université d'Orléans; 2010. [cited 2021 Jan 15]. Available from: http://www.theses.fr/2010ORLE2050.

Council of Science Editors:

Pesnel S. Développement de modalités d'imagerie in vivo pour l'oncologie expérimentale. : Development of in vivo imaging modalities for experimental oncology. [Doctoral Dissertation]. Université d'Orléans; 2010. Available from: http://www.theses.fr/2010ORLE2050

4. Caillé, Fabien. Synthèse et caractérisation de sondes bimodales pour l'IRM et l'imagerie optique : Synthesis and characterization of bimodal probes for MRI and optical imaging.

Degree: Docteur es, Chimie, 2011, Université d'Orléans

URL: http://www.theses.fr/2011ORLE2033

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L’Imagerie par Résonance Magnétique (IRM) offre une excellente résolution à l’échelle macroscopique alors que l’imagerie optique lui est parfaitement complémentaire car elle dispose d’une haute… (more)

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L’Imagerie par Résonance Magnétique (IRM) offre une excellente résolution à l’échelle macroscopique alors que l’imagerie optique lui est parfaitement complémentaire car elle dispose d’une haute résolution à l’échelle microscopique ainsi que d’une forte sensibilité. Les complexes de gadolinium(III) ont déjà prouvé leur efficacité en tant qu’agents de contraste IRM et d’autres lanthanides luminescents émettant dans le proche infrarouge conviennent pour l’imagerie optique. Des complexes de lanthanides bishydratés à motif pyridine montrant des résultats très prometteurs pour les deux types d’imagerie ont été développés précédemment au laboratoire. Afin d’améliorer leurs propriétés optiques, des ligands à motifs isoquinoléines ont été synthétisés. Leurs complexes de lanthanides montrent des propriétés magnétiques prometteuses et des constantes thermodynamiques qui démontrent leur faible toxicité in vitro. La longueur d’onde d’excitation et les rendements quantiques des complexes d’Yb3+ et de Nd3+ ont été augmentés pour permettre d’obtenir des images de luminescence et d’envisager des applications in vivo.Afin d’améliorer davantage ces propriétés optiques, la synthèse de ligands à motif 2-azaanthraquinone a été entreprise mais l’instabilité chimique de ces molécules n’a pas permis d’isoler les ligands désirés.Cette approche bimodale a été appliquée à la conception de sondes sensibles au zinc. La synthèse de complexes de Gd3+ à motifs pyridines adaptés permet une detection relaxométrique qualitative et sélective de ce cation. Cependant, l’absence de variation du nombre d’hydratation ne permet pas la détection par luminescence. De légères modifications chimiques sur les ligands devraient permettre d’atteindre cet objectif.

Among the state-of-the-art imaging techniques, Magnetic Resonance Imaging (MRI) offers an excellent macroscopic scale resolution whereas optical imaging shows high microscopic scale resolution and great sensitivity. Gadolinium complexes have already proved their efficiency as MRI contrast agents whereas other lanthanide cations emitting in the near infrared may suit for optical imaging purposes. Pyridine-based lanthanide complexes which showed promising results as bimodal probes have previously been developed. In the objective of improving their optical properties, isoquinoline-based ligands have been synthesized. The lanthanide complexes show promising magnetic properties and their thermodynamic stability presumes in vitro low toxicity. Excitation wavelengths and quantum yields of both Nd3+ and Yb3+ complexes have been improved to obtain luminescence images and to foresee in vivo applications. In order to further improve the optical properties, attempts to synthesize 2-azaanthraquinone-based ligands have been made.The desired ligands could not have been isolated due to their chemical instability. This bimodal approach has been applied to the design of smart probes sensitive to zinc. The qualitative and selective detection of the latter has been realized thanks to Gd3+ complexes with adapted…

Advisors/Committee Members: Suzenet, Franck (thesis director), Jakab-Toth, Eva (thesis director).

Subjects/Keywords: Sondes bimodales; Sondes d'imagerie; 2-azaanthraquinone; Bimodal probes; Imaging probes; 2-azaanthraquinone

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APA (6^th Edition):

Caillé, F. (2011). Synthèse et caractérisation de sondes bimodales pour l'IRM et l'imagerie optique : Synthesis and characterization of bimodal probes for MRI and optical imaging. (Doctoral Dissertation). Université d'Orléans. Retrieved from http://www.theses.fr/2011ORLE2033

Chicago Manual of Style (16^th Edition):

Caillé, Fabien. “Synthèse et caractérisation de sondes bimodales pour l'IRM et l'imagerie optique : Synthesis and characterization of bimodal probes for MRI and optical imaging.” 2011. Doctoral Dissertation, Université d'Orléans. Accessed January 15, 2021. http://www.theses.fr/2011ORLE2033.

MLA Handbook (7^th Edition):

Caillé, Fabien. “Synthèse et caractérisation de sondes bimodales pour l'IRM et l'imagerie optique : Synthesis and characterization of bimodal probes for MRI and optical imaging.” 2011. Web. 15 Jan 2021.

Vancouver:

Caillé F. Synthèse et caractérisation de sondes bimodales pour l'IRM et l'imagerie optique : Synthesis and characterization of bimodal probes for MRI and optical imaging. [Internet] [Doctoral dissertation]. Université d'Orléans; 2011. [cited 2021 Jan 15]. Available from: http://www.theses.fr/2011ORLE2033.

Council of Science Editors:

Caillé F. Synthèse et caractérisation de sondes bimodales pour l'IRM et l'imagerie optique : Synthesis and characterization of bimodal probes for MRI and optical imaging. [Doctoral Dissertation]. Université d'Orléans; 2011. Available from: http://www.theses.fr/2011ORLE2033

Western Carolina University

5. Sedberry, Seth Alexander. Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer.

Degree: 2016, Western Carolina University

URL: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21232

► A multi-part fluorescent probe was designed for the development of new clinical tools for the detection and treatment of melanoma skin cancer. It has been… (more)

Subjects/Keywords: Fluorescent probes; Luminescent probes; Fluorescence spectroscopy; Melanoma – Early detection; Imaging systems in biology

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APA (6^th Edition):

Sedberry, S. A. (2016). Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer. (Masters Thesis). Western Carolina University. Retrieved from http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21232

Chicago Manual of Style (16^th Edition):

Sedberry, Seth Alexander. “Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer.” 2016. Masters Thesis, Western Carolina University. Accessed January 15, 2021. http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21232.

MLA Handbook (7^th Edition):

Sedberry, Seth Alexander. “Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer.” 2016. Web. 15 Jan 2021.

Vancouver:

Sedberry SA. Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer. [Internet] [Masters thesis]. Western Carolina University; 2016. [cited 2021 Jan 15]. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21232.

Council of Science Editors:

Sedberry SA. Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer. [Masters Thesis]. Western Carolina University; 2016. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21232

6. NC DOCKS at Western Carolina University; Sedberry, Seth Alexander. Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer.

Degree: 2016, NC Docks

URL: http://libres.uncg.edu/ir/wcu/f/Sedberry2016.pdf

► A multi-part fluorescent probe was designed for the development of new clinical tools for the detection and treatment of melanoma skin cancer. It has been… (more)

Subjects/Keywords: Fluorescent probes; Luminescent probes; Fluorescence spectroscopy; Melanoma – Early detection; Imaging systems in biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

NC DOCKS at Western Carolina University; Sedberry, S. A. (2016). Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer. (Thesis). NC Docks. Retrieved from http://libres.uncg.edu/ir/wcu/f/Sedberry2016.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

NC DOCKS at Western Carolina University; Sedberry, Seth Alexander. “Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer.” 2016. Thesis, NC Docks. Accessed January 15, 2021. http://libres.uncg.edu/ir/wcu/f/Sedberry2016.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

NC DOCKS at Western Carolina University; Sedberry, Seth Alexander. “Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer.” 2016. Web. 15 Jan 2021.

Vancouver:

NC DOCKS at Western Carolina University; Sedberry SA. Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer. [Internet] [Thesis]. NC Docks; 2016. [cited 2021 Jan 15]. Available from: http://libres.uncg.edu/ir/wcu/f/Sedberry2016.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

NC DOCKS at Western Carolina University; Sedberry SA. Synthesis and characterization of time-resolved fluorescence probes for the potential detection and improved study of melanoma cancer. [Thesis]. NC Docks; 2016. Available from: http://libres.uncg.edu/ir/wcu/f/Sedberry2016.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

NSYSU

7. Liou, Sz-Yu. The Structural Modification of Conjugated Polymers for the Development of Near Infrared Fluorescing Semiconducting Polymer Dots for Bioimaging.

Degree: Master, Chemistry, 2015, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0029115-113715

► In recent years, semiconducting polymer dots (Pdots) have emerged as a new class of extraordinarily bright fluorescent probes with innovative applications in biological imaging and… (more)

Subjects/Keywords: Semiconducting Polymer dots; Near Infrared; Fluorescent Probes; Bioimaging; Fluorescent imaging

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Liou, S. (2015). The Structural Modification of Conjugated Polymers for the Development of Near Infrared Fluorescing Semiconducting Polymer Dots for Bioimaging. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0029115-113715

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Liou, Sz-Yu. “The Structural Modification of Conjugated Polymers for the Development of Near Infrared Fluorescing Semiconducting Polymer Dots for Bioimaging.” 2015. Thesis, NSYSU. Accessed January 15, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0029115-113715.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Liou, Sz-Yu. “The Structural Modification of Conjugated Polymers for the Development of Near Infrared Fluorescing Semiconducting Polymer Dots for Bioimaging.” 2015. Web. 15 Jan 2021.

Vancouver:

Liou S. The Structural Modification of Conjugated Polymers for the Development of Near Infrared Fluorescing Semiconducting Polymer Dots for Bioimaging. [Internet] [Thesis]. NSYSU; 2015. [cited 2021 Jan 15]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0029115-113715.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Liou S. The Structural Modification of Conjugated Polymers for the Development of Near Infrared Fluorescing Semiconducting Polymer Dots for Bioimaging. [Thesis]. NSYSU; 2015. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0029115-113715

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

McMaster University

8. Albu, Silvia + A. THE SYNTHESIS AND EVALUATION OF SMALL MOLECULE INHIBITORS AS MOLECULAR IMAGING AGENTS FOR UROKINASE PLASMINOGEN ACTIVATOR.

Degree: PhD, 2015, McMaster University

URL: http://hdl.handle.net/11375/16601

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Urokinase-type plasminogen activator (uPA) protein is a serine protease of the trypsin family that is overexpressed by tumors cells seeking to metastasize. Molecular imaging methods… (more)

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Urokinase-type plasminogen activator (uPA) protein is a serine protease of the trypsin family that is overexpressed by tumors cells seeking to metastasize. Molecular imaging methods using molecular imaging probe designed to target uPA could provide a method for the detection of aggressive cancers and monitoring response to treatment. Four classes of high affinity uPA inhibitors, three which were reversible and one irreversible, were used as platforms to develop radiolabeled probes for uPA. Based on structure-activity relationships, lead compounds were modified to allow for the introduction of a radiohalogen (radioiodine) at different sites in the corresponding molecules. Suitable synthetic strategies were developed to create libraries of iodinated phenyl guanidine, peptide, naphtamidine and phosphonate derivatives. For the phenylguanidines colorimetric assays showed the product had micromolar affinity while for the peptide derivatives low nanomolar affinity for the iodinated analogue was observed (1.4 nM to 2.53 nM). Unfortunately quantitative biodistribution studies showed low tumour uptake (<0.5% ID/g). More promising results were obtained for the irreversible iodinated phosphonated derivative which had an affinity of 2.1 nM. This reagent showed 1.95% ID/g tumour uptake and lower blood uptake in vivo which demonstrates advantageous properties over existing uPA probes in terms of tumour-to-blood ratios. A complementary development was also achieved in that the first example of a 125I-labelled tetrazine was prepared. This new reagent can be used in pre-targeted strategies that utilize bioorthogonal coupling between stained trans-cyclooctene (TCO) and tetrazines. The product was prepared using a concomitant oxidation iodo-destannylation reaction and the product isolated in 80% radiochemical yield. The reaction with transcycloctene proceeded rapidly to produce various isomers which were fully characterized through NMR analysis of the non-radioactive analogues.

Thesis

Doctor of Philosophy (PhD)

Advisors/Committee Members: Capretta, Alfredo, Valliant, John, Chemical Biology.

Subjects/Keywords: Urokinase-type plasminogen activator; Molecular imaging probes; 125I-labelled tetrazine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Albu, S. +. A. (2015). THE SYNTHESIS AND EVALUATION OF SMALL MOLECULE INHIBITORS AS MOLECULAR IMAGING AGENTS FOR UROKINASE PLASMINOGEN ACTIVATOR. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/16601

Chicago Manual of Style (16^th Edition):

Albu, Silvia + A. “THE SYNTHESIS AND EVALUATION OF SMALL MOLECULE INHIBITORS AS MOLECULAR IMAGING AGENTS FOR UROKINASE PLASMINOGEN ACTIVATOR.” 2015. Doctoral Dissertation, McMaster University. Accessed January 15, 2021. http://hdl.handle.net/11375/16601.

MLA Handbook (7^th Edition):

Albu, Silvia + A. “THE SYNTHESIS AND EVALUATION OF SMALL MOLECULE INHIBITORS AS MOLECULAR IMAGING AGENTS FOR UROKINASE PLASMINOGEN ACTIVATOR.” 2015. Web. 15 Jan 2021.

Vancouver:

Albu S+A. THE SYNTHESIS AND EVALUATION OF SMALL MOLECULE INHIBITORS AS MOLECULAR IMAGING AGENTS FOR UROKINASE PLASMINOGEN ACTIVATOR. [Internet] [Doctoral dissertation]. McMaster University; 2015. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/11375/16601.

Council of Science Editors:

Albu S+A. THE SYNTHESIS AND EVALUATION OF SMALL MOLECULE INHIBITORS AS MOLECULAR IMAGING AGENTS FOR UROKINASE PLASMINOGEN ACTIVATOR. [Doctoral Dissertation]. McMaster University; 2015. Available from: http://hdl.handle.net/11375/16601

University of Miami

9. Cauley, Anthony Nolan. Fluorophores in Confined Spaces: From Targeting Molecular Transporters to Encapsulation by Organic Nanocontainers.

Degree: PhD, Chemistry (Arts and Sciences), 2018, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/2023

► Fluorescence is achieved by emission of electromagnetic radiation in the form of ultraviolet, visible, or infrared photons as a result of an electronic transition… (more)

▼ Fluorescence is achieved by emission of electromagnetic radiation in the form of ultraviolet, visible, or infrared photons as a result of an electronic transition from singlet excited state to singlet ground state. Fluorescence spectroscopy is a widely utilized technique for studying the structure and dynamics of matter and living systems. It may come in many forms such as small organic fluorophores taking on a “drug-like” role in biological organisms as well as supramolecular host-guest complexes for applications in drug delivery and cellular imaging. Herein, two research projects at the interface of chemistry and biology will be fully discussed. Although the two ventures have different goals, the overarching theme is confining fluorescent molecules in a tight space, such as a transporter or organic nanoparticle, to enhance the optical properties by restricting motion and limiting solvent accessibility. First, a series of stilbene derivatives were synthesized and investigated as substrates targeting monoamine transporters (MATs). The sensitivity of these fluorescent probes allows binding-induced fluorescence based on their ability to access a twisted intramolecular charge transfer (TICT) state. The photophysical properties of the dyes were studied in solvents differing in polarity and viscosity to model their response and translate this behavior to a binding event. The lack of specificity to the MAT target lead to their use as generic cell membrane stains, comparable to that of a commercially available, widely used dye in biological laboratories. Also, a library of functionalized lignins is reported to demonstrate their utility as nanocontainers for organic dyes in biologically relevant applications. Kraft lignin was modified via SN2 reaction at the phenolic -OH group utilizing a mild base, potassium carbonate, and various alkyl halides, several bearing additional functionalities, with dimethylsulfoxide as solvent. The resulting phenoxy ethers were characterized by 1H- NMR and IR spectroscopy, as well as DLS and SEM to evaluate their morphology and supramolecular organization. Lignin modified with long-chain hydrocarbon tails was found to effectively encapsulate DiD, a cyanine dye, decrease aggregation, enhance optical transitions, and exert a photoprotective effect. The dye-lignin assemblies were also examined as imaging agents, via confocal microscopy, and found to accumulate intracellularly with no leaching of the dye to hydrophobic subcellular components observed. Lignin functionalized with short chain carboxylic acids interacts with ligands directed at the norepinephrine transporter (NET), suggesting applications in sequestration of neuroactive compounds. Lignin nanocontainers can also be employed in other applications such as coatings for cell culture vessels, ion-sensitive cargo release, energy transfer between guest molecules, and specific drug delivery targeting the biotin transport system. This comprehensive list of applications utilizing lignin proves its worth as a nanomaterial in a biomedical… Advisors/Committee Members: James N. Wilson, Francisco M. Raymo, Marc R. Knecht, Ryan L. Karkkainen.

Subjects/Keywords: fluorescence; fluorescent probes; monoamine transporters; lignin; nanocontainers; cellular imaging

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cauley, A. N. (2018). Fluorophores in Confined Spaces: From Targeting Molecular Transporters to Encapsulation by Organic Nanocontainers. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/2023

Chicago Manual of Style (16^th Edition):

Cauley, Anthony Nolan. “Fluorophores in Confined Spaces: From Targeting Molecular Transporters to Encapsulation by Organic Nanocontainers.” 2018. Doctoral Dissertation, University of Miami. Accessed January 15, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/2023.

MLA Handbook (7^th Edition):

Cauley, Anthony Nolan. “Fluorophores in Confined Spaces: From Targeting Molecular Transporters to Encapsulation by Organic Nanocontainers.” 2018. Web. 15 Jan 2021.

Vancouver:

Cauley AN. Fluorophores in Confined Spaces: From Targeting Molecular Transporters to Encapsulation by Organic Nanocontainers. [Internet] [Doctoral dissertation]. University of Miami; 2018. [cited 2021 Jan 15]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/2023.

Council of Science Editors:

Cauley AN. Fluorophores in Confined Spaces: From Targeting Molecular Transporters to Encapsulation by Organic Nanocontainers. [Doctoral Dissertation]. University of Miami; 2018. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/2023

Rice University

10. Schweller, Ryan. Development of Dynamic DNA Probes for High-Content in situ Proteomic Analyses.

Degree: PhD, Engineering, 2012, Rice University

URL: http://hdl.handle.net/1911/64649

► Dynamic DNA complexes are able to undergo multiple hybridization and dissociation events through a process called strand displacement. This unique property has facilitated the creation… (more)

▼ Dynamic DNA complexes are able to undergo multiple hybridization and dissociation events through a process called strand displacement. This unique property has facilitated the creation of programmable molecular detection systems and chemical logic gates encoded by nucleotide sequence. This work examines whether the ability to selective exchange oligonucleotides among different thermodynamically-stable DNA complexes can be harnessed to create a new class of imaging probes that permit fluorescent reporters to be sequentially activated (“turned on”) and erased (“turned off”). Here, dynamic DNA complexes detect a specific DNA-conjugated antibody and undergo strand displacement to liberate a quencher strand and activate a fluorescent reporter. Subsequently, incubation with an erasing complex allows the fluorophore to be stripped from the target strand, quenched, and washed away. This simple capability therefore allows the same fluorescent dyes to be used multiple times to detect different markers within the same sample via sequential rounds of fluorescence imaging. We evaluated and optimized several DNA complex designs to function efficiently for in situ molecular analyses. We also applied our DNA probes to immunofluorescence imaging using DNA-conjugated antibodies and demonstrated the ability to at least double the number of detectable markers on a single sample. Finally, the probe complexes were reconfigured to act as AND-gates for the detection of co-localized proteins. Given the ability to visualize large numbers of cellular markers using dynamic DNA probe complexes, high-content proteomic analyses can be performed on a single sample, enhancing the power of fluorescence imaging techniques. Furthermore, dynamic DNA complexes offer new avenues to incorporate DNA-based computations and logic for in situ molecular imaging and analyses. Advisors/Committee Members: Diehl, Michael R. (advisor), Qutub, Amina A. (committee member), Farach-Carson, Cindy (committee member).

Subjects/Keywords: DNA nanotechnology; Molecular imaging; Strand displacement; Nucleic acids; Fluorescent probes; Immunochemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schweller, R. (2012). Development of Dynamic DNA Probes for High-Content in situ Proteomic Analyses. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/64649

Chicago Manual of Style (16^th Edition):

Schweller, Ryan. “Development of Dynamic DNA Probes for High-Content in situ Proteomic Analyses.” 2012. Doctoral Dissertation, Rice University. Accessed January 15, 2021. http://hdl.handle.net/1911/64649.

MLA Handbook (7^th Edition):

Schweller, Ryan. “Development of Dynamic DNA Probes for High-Content in situ Proteomic Analyses.” 2012. Web. 15 Jan 2021.

Vancouver:

Schweller R. Development of Dynamic DNA Probes for High-Content in situ Proteomic Analyses. [Internet] [Doctoral dissertation]. Rice University; 2012. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/1911/64649.

Council of Science Editors:

Schweller R. Development of Dynamic DNA Probes for High-Content in situ Proteomic Analyses. [Doctoral Dissertation]. Rice University; 2012. Available from: http://hdl.handle.net/1911/64649

11. Elajaili, Hanan B. Electron Paramagnetic Resonance Imaging and Probes.

Degree: PhD, Chemistry and Biochemistry, 2014, U of Denver

URL: https://digitalcommons.du.edu/etd/179

► EPR imaging at low frequency is an important method to measure in vivo physiology. Because native paramagnetic species exist at low concentrations in living… (more)

▼ EPR imaging at low frequency is an important method to measure in vivo physiology. Because native paramagnetic species exist at low concentrations in living systems, exogenous paramagnetic species are needed for in vivo EPR. Selection of the appropriate EPR probe allows the experimenter to obtain information about the environment of the imaged probe and its spatial distribution. Relaxation times for several nitroxide radicals were studied with the aim of understanding the relaxation mechanisms, which provides criteria for design of suitable in vivo imaging probes. Amino-substituted trityl radicals have the potential to monitor pH in vivo, and the suitability for this application depends on spectral properties. Electron spin relaxation times T₁ and T₂ were measured at X-band for the protonated and deprotonated forms of two amino-substituted triaryl methyl radicals. T₁ exhibits little dependence on protonation, which makes it useful for measuring O₂ concentration. Values of T₂ vary substantially with pH, reflecting a range of dynamic processes, and thus T₂ is a potentially useful monitor of pH. The spin-lattice relaxation rates at 293 K for three anionic semiquinones (2,5-di-t-butyl-1,4-benzosemiquinone, 2,6-di-t-butyl-1,4-benzosemiquinone, and 2,3,5,6-tetramethoxy-1,4-benzosemiquinone) were studied at up to 8 frequencies between 250 MHz and 34 GHz in ethanol or methanol solution containing high concentrations of OH^-. The relaxation rates are about a factor of 2 faster at lower frequencies than at 9 or 34 GHz when measured in solvent with normal isotope abundance. However, in perdeuterated alcohols the relaxation rates exhibit little frequency dependence. The relaxation rates were modeled as the sum of two frequency-independent contributions (spin rotation and a local mode) and two frequency-dependent contributions (modulation of dipolar interaction with solvent nuclei and a much smaller contribution from modulation of g anisotropy). The correlation time for modulation of the interaction with solvent nuclei is longer than the tumbling correlation time and is attributed to hydrogen bonding of the alcohol to the oxygen atoms of the semiquinones. Rapid scan imaging was shown, for the same data acquisition time, to give higher signal-to-noise than continuous wave for the nitroxide probe ¹⁵N-perdeuterated tempone. The narrow spectral widths for the amino-substituted triaryl methyl radicals facilitate spectral-spatial EPR imaging. A phantom was imaged using rapid scan to test the feasibility of mapping the pH and to test a new algorithm for full spectrum imaging. Finally, a spin coherence phenomenon was observed at X-band in semiquinone rapid scan spectra, which arises from closely-spaced nuclear hyperfine lines. Advisors/Committee Members: Sandra S. Eaton, Ph.D..

Subjects/Keywords: Electron paramagnetic resonance; Imaging; Probes; Chemistry; Physical Sciences and Mathematics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Elajaili, H. B. (2014). Electron Paramagnetic Resonance Imaging and Probes. (Doctoral Dissertation). U of Denver. Retrieved from https://digitalcommons.du.edu/etd/179

Chicago Manual of Style (16^th Edition):

Elajaili, Hanan B. “Electron Paramagnetic Resonance Imaging and Probes.” 2014. Doctoral Dissertation, U of Denver. Accessed January 15, 2021. https://digitalcommons.du.edu/etd/179.

MLA Handbook (7^th Edition):

Elajaili, Hanan B. “Electron Paramagnetic Resonance Imaging and Probes.” 2014. Web. 15 Jan 2021.

Vancouver:

Elajaili HB. Electron Paramagnetic Resonance Imaging and Probes. [Internet] [Doctoral dissertation]. U of Denver; 2014. [cited 2021 Jan 15]. Available from: https://digitalcommons.du.edu/etd/179.

Council of Science Editors:

Elajaili HB. Electron Paramagnetic Resonance Imaging and Probes. [Doctoral Dissertation]. U of Denver; 2014. Available from: https://digitalcommons.du.edu/etd/179

Western Carolina University

12. Martin, Louis Christopher. Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications.

Degree: 2016, Western Carolina University

URL: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21208

► Lanthanide-based materials are attractive candidates for the use in light emitting devices, immunoassays, and in-vitro cellular imaging technologies. Their superior luminescent properties include sharp emission… (more)

Subjects/Keywords: Rare earth metals – Imaging; Fluorescence spectroscopy; Luminescent probes; Silica

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APA (6^th Edition):

Martin, L. C. (2016). Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications. (Masters Thesis). Western Carolina University. Retrieved from http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21208

Chicago Manual of Style (16^th Edition):

Martin, Louis Christopher. “Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications.” 2016. Masters Thesis, Western Carolina University. Accessed January 15, 2021. http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21208.

MLA Handbook (7^th Edition):

Martin, Louis Christopher. “Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications.” 2016. Web. 15 Jan 2021.

Vancouver:

Martin LC. Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications. [Internet] [Masters thesis]. Western Carolina University; 2016. [cited 2021 Jan 15]. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21208.

Council of Science Editors:

Martin LC. Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications. [Masters Thesis]. Western Carolina University; 2016. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=21208

13. Martin, Louis Christopher. Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications.

Degree: 2016, NC Docks

URL: http://libres.uncg.edu/ir/wcu/f/Martin2016.pdf

► Lanthanide-based materials are attractive candidates for the use in light emitting devices, immunoassays, and in-vitro cellular imaging technologies. Their superior luminescent properties include sharp emission… (more)

Subjects/Keywords: Rare earth metals – Imaging; Fluorescence spectroscopy; Luminescent probes; Silica

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APA (6^th Edition):

Martin, L. C. (2016). Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications. (Thesis). NC Docks. Retrieved from http://libres.uncg.edu/ir/wcu/f/Martin2016.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Martin, Louis Christopher. “Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications.” 2016. Thesis, NC Docks. Accessed January 15, 2021. http://libres.uncg.edu/ir/wcu/f/Martin2016.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Martin, Louis Christopher. “Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications.” 2016. Web. 15 Jan 2021.

Vancouver:

Martin LC. Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications. [Internet] [Thesis]. NC Docks; 2016. [cited 2021 Jan 15]. Available from: http://libres.uncg.edu/ir/wcu/f/Martin2016.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Martin LC. Synthesis and characterization of Ln(BTFA)3DMPHEN complexes (Ln= Eu3+, Er3+, Ho3+, Tb3+, Tm3+,AND Yb3+, BTFA=4,4,4-triflouro-1-phenyl-1,3-butanedione,dmphen=4,7-dimethyl-1,10-phenathroline) and sol-gel materials for potential optical applications. [Thesis]. NC Docks; 2016. Available from: http://libres.uncg.edu/ir/wcu/f/Martin2016.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Louisiana State University

14. Hettiarachchi, Suraj Uditha. Design, Synthesis, and Evaluation of Small Molecule-based, Profluorogenic Activatable Substrate Probes for Detection and Visualization of Human Cancer Enzyme NAD(P)H:Quinone Oxidoreductase-1.

Degree: PhD, Chemistry, 2014, Louisiana State University

URL: etd-02192015-200616 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3269

► Cancer comprises many specific diseases, and it is currently responsible for millions of deaths worldwide. This broad disease profile is a great challenge for… (more)

▼ Cancer comprises many specific diseases, and it is currently responsible for millions of deaths worldwide. This broad disease profile is a great challenge for personalized oncology. Critical for the success of cancer therapy is the exploration of improved methodologies for the early detection of localized and disseminated tumor cells in patients, where bio-molecular imaging has become an indispensable tool. Being one of many different imaging techniques, optical fluorescence imaging has been translated over the years from the bench to clinical research, and it is now on the verge of being able to address some of the pressing challenges in molecular oncology. Optical imaging can provide real-time, high spatially and temporally resolved detection of small cancer foci or establishment of boundaries between malignant and normal tissue during surgery, which is the primary treatment modality for most solid tumors. Furthermore, optical signals can provide information on tumor metabolism and biochemistry that helps provide an understanding of tumors at the molecular level, so as to gain access to the activity of their biological processes that may yield the capability to provide personalized “on the spot” treatment.Thus, advancing development of new optical fluorescent probes for imaging techniques has grown exponentially over the years, as these probes continue to revolutionize the ability to visualize complex biological processes in living systems. Fluorophores have been used in a wide variety of applications, ranging from medical diagnostic applications as chemical sensors and molecular probes, to display devices and dye-sensitized solar cells. Although extensive research work has been done on the development of molecular imaging probes, their use in the clinical setting is still in its infancy. The number of profluorophores that can have their fluorescence signature selectively and quickly altered by the presence of a disease-associated enzyme is extremely small, as is the type of disease-associated enzyme used for probe activation. The goal of this thesis is development of a group of small molecule-based profluorogenic probes and demonstration of their activity with a cancer-associated enzyme, NAD(P)H:quinone oxidoreductase-1 (NQO1). This goal was attained by completing several different objectives that will be discussed together with their outcomes in the following chapters of this dissertation.

Subjects/Keywords: Fluorescence guided surgery; Imaging probes; NQO1; PeT; self-immolative; Trimethyl lock

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APA (6^th Edition):

Hettiarachchi, S. U. (2014). Design, Synthesis, and Evaluation of Small Molecule-based, Profluorogenic Activatable Substrate Probes for Detection and Visualization of Human Cancer Enzyme NAD(P)H:Quinone Oxidoreductase-1. (Doctoral Dissertation). Louisiana State University. Retrieved from etd-02192015-200616 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3269

Chicago Manual of Style (16^th Edition):

Hettiarachchi, Suraj Uditha. “Design, Synthesis, and Evaluation of Small Molecule-based, Profluorogenic Activatable Substrate Probes for Detection and Visualization of Human Cancer Enzyme NAD(P)H:Quinone Oxidoreductase-1.” 2014. Doctoral Dissertation, Louisiana State University. Accessed January 15, 2021. etd-02192015-200616 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3269.

MLA Handbook (7^th Edition):

Hettiarachchi, Suraj Uditha. “Design, Synthesis, and Evaluation of Small Molecule-based, Profluorogenic Activatable Substrate Probes for Detection and Visualization of Human Cancer Enzyme NAD(P)H:Quinone Oxidoreductase-1.” 2014. Web. 15 Jan 2021.

Vancouver:

Hettiarachchi SU. Design, Synthesis, and Evaluation of Small Molecule-based, Profluorogenic Activatable Substrate Probes for Detection and Visualization of Human Cancer Enzyme NAD(P)H:Quinone Oxidoreductase-1. [Internet] [Doctoral dissertation]. Louisiana State University; 2014. [cited 2021 Jan 15]. Available from: etd-02192015-200616 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3269.

Council of Science Editors:

Hettiarachchi SU. Design, Synthesis, and Evaluation of Small Molecule-based, Profluorogenic Activatable Substrate Probes for Detection and Visualization of Human Cancer Enzyme NAD(P)H:Quinone Oxidoreductase-1. [Doctoral Dissertation]. Louisiana State University; 2014. Available from: etd-02192015-200616 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3269

University of Sydney

15. Kaur, Amandeep. Fluorescent tools for imaging oxidative stress in biology .

Degree: 2016, University of Sydney

URL: http://hdl.handle.net/2123/15063

► Oxidative stress has been implicated in a myriad of pathological conditions, but measuring it and deciphering the underlying the mechanisms has been a long-standing challenge.… (more)

▼ Oxidative stress has been implicated in a myriad of pathological conditions, but measuring it and deciphering the underlying the mechanisms has been a long-standing challenge. Most of the existing redox probes are reaction-based and irreversible. In contrast, reversible redox probes with biologically-tuned redox potential can distinguish between transient and chronic elevations in oxidative capacity. In this work, a series of novel fluorescent redox probes based on flavins and nicotinamides have been developed and tested. The first redox-responsive probe, NpFR1, localises in the cytoplasm and exhibits robust reversibility of oxidation and reduction and a clear fluorescence increase upon oxidation. Based on these promising results, attention turned to developing analogues of NpFR1, with two main aims: to send the probe to the specific sub-cellular organelles, and to develop a ratiometric probe, in which a change in redox state was signalled by a change in colour rather than fluorescence intensity. To this end, six further probes were developed. A mitochondrially-localising derivative NpFR2 was developed by incorporating a lipophilic cationic tag. The design of the emission-ratiometric redox probe FCR1 whose fluorescence emission changes from blue to green upon oxidation, is based on the FRET process between coumarin donor and flavin acceptor. Furthermore, a set of excitation-ratiometric FRET probes FRR1 and FRR2 were developed, in which mitochondrial targeting was achieved by employing rhodamine B with inherent mitochondrial accumulation properties. Finally, nicotinamide-based redox probes NCR3 and NCR4 demonstrate the use of ICT as a strategy to attain ratiometric fluorescence properties. Following the successful utilisation of ratiometric and targeting strategies, the developed probes were applied in a variety of biological investigations, whether in cellulo, ex vivo or non-mammalian systems. The probes demonstrated excellent abilities to report on the differences in oxidative capacities under different conditions within each system. This work therefore demonstrates that reversible redox probes based on flavins and nicotinamides exhibit suitable properties for use as cellular redox probes. The developed probes can be modulated to give ratiometric output and targeted to specific sub-cellular compartments. These probes therefore exhibit potential to aid in deciphering the role of oxidative stress in pathogenesis and disease progression.

Subjects/Keywords: Chemosensor; Fluorescence; molecular imaging; oxidative stress; reactive oxygen species; responsive probes

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APA (6^th Edition):

Kaur, A. (2016). Fluorescent tools for imaging oxidative stress in biology . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/15063

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kaur, Amandeep. “Fluorescent tools for imaging oxidative stress in biology .” 2016. Thesis, University of Sydney. Accessed January 15, 2021. http://hdl.handle.net/2123/15063.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kaur, Amandeep. “Fluorescent tools for imaging oxidative stress in biology .” 2016. Web. 15 Jan 2021.

Vancouver:

Kaur A. Fluorescent tools for imaging oxidative stress in biology . [Internet] [Thesis]. University of Sydney; 2016. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/2123/15063.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kaur A. Fluorescent tools for imaging oxidative stress in biology . [Thesis]. University of Sydney; 2016. Available from: http://hdl.handle.net/2123/15063

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Georgia Tech

16. Alonas, Eric James. Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2015, Georgia Tech

URL: http://hdl.handle.net/1853/56173

► A method for labeling the genomic RNA of the human respiratory syncytial virus, as well as for isolating and examining the labeled filamentous virions was… (more)

Subjects/Keywords: RSV; RNA imaging; Live cell imaging; dSTORM; STED; Cryo-ET; TEM; RNA virus; RNA probes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alonas, E. J. (2015). Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/56173

Chicago Manual of Style (16^th Edition):

Alonas, Eric James. “Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy.” 2015. Doctoral Dissertation, Georgia Tech. Accessed January 15, 2021. http://hdl.handle.net/1853/56173.

MLA Handbook (7^th Edition):

Alonas, Eric James. “Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy.” 2015. Web. 15 Jan 2021.

Vancouver:

Alonas EJ. Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/1853/56173.

Council of Science Editors:

Alonas EJ. Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/56173

17. Gondrand, Corentin. Étude chémobiologique de sondes magnétogènes et fluorogènes pour l'imagerie moléculaire : Magnetogenic and fluorogenic probes for molecular imaging : a chemical biology study.

Degree: Docteur es, Chimie, 2016, Lyon

URL: http://www.theses.fr/2016LYSEN070

►

Cette thèse de doctorat traite de la conception et de l’évaluation de sondes magnétogènes et fluorogènes pour la détection in vivo d’activités enzymatiques.Des molécules capables… (more)

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Cette thèse de doctorat traite de la conception et de l’évaluation de sondes magnétogènes et fluorogènes pour la détection in vivo d’activités enzymatiques.Des molécules capables d’acquérir un moment magnétique à partir d’un état diamagnétique et en réponse à l’action d’une enzyme seraient d’un grand intérêt pour l’imagerie moléculaire par résonance magnétique. Deux exemples de telles sondes magnétogéniques avaient été mis au point précédemment, l’un pouvant opérer en conditions physiologiques, l’autre nécessitant une acidification du milieu pour devenir paramagnétique. En préparant de nouveaux analogues du premier exemple, j’ai pu trouver une molécule dont la fragmentation a lieu trois fois plus rapidement que la molécule originale. J’ai ensuite travaillé à la conception de sondes dérivées du deuxième exemple et répondant à des activités enzymatiques ; de telles molécules permettraient de réaliser la quantification in vitro d’une activité enzymatique à des fins diagnostiques. À ce titre, j’ai participé à l’élaboration de deux preuves de concept de dispositifs dédiés à la mesure du temps de relaxation longitudinale de micro-volumes. J’ai enfin entamé le développement de nouveaux complexes s’inspirant du second exemple mais capables de fonctionner dans le milieu biologique.Le deuxième volet de mes travaux porte sur la réalisation de sondes fluorogènes précipitantes pour des activités glycosidases. Une sonde pour la leucine aminopeptidase profitant des propriétés exceptionnelles de stabilité, de luminescence et de solubilité du fluorophore ELF®-97 avaient démontré une grande efficacité pour marquer rapidement des cellules HeLa. J’ai mis au point une nouvelle architecture de sondes qui permet le ciblage de glycosidases via l’utilisation d’un tandem d’espaceurs cyclisants. Deux sondes ont été préparées, l’une pour la beta-galactosidase, l’autre pour la cellulase. La première a prouvé son bon fonctionnement pour marquer les cellules exprimant l’enzyme en bénéficiant d’une grande sensibilité. La seconde a pu être utilisée pour quantifier l’activité cellulase sécrétée par des levures, avec l’objectif d’obtenir un moyen économiquement intéressant de produire du bioéthanol à partir des déchets végétaux.

This PhD thesis deals with the design and evaluation of magnetogenic and fluorogenic probes for the in vivo detection of enzyme activities.Molecules capable of switching from a diamagnetic to a paramagnetic state in response to an enzyme stimulus would be of great interest for molecular magnetic resonance imaging. Two examples of such magnetogenic probes had been designed in a previous work : one can operate in physiological conditions, whereas the other needs an acidification of the water medium to become paramagnetic. I prepared new analogues of the first probe ; one molecule displayed fragmentation three times faster than the original compound. Then I designed and synthesized probes derived from the second example and responsive to enzyme activities ; such molecules are suitable for the in vitro quantification of enzyme…

Advisors/Committee Members: Hasserodt, Jens (thesis director).

Subjects/Keywords: Chimie biologique; Sondes magnétogènes; Sondes fluorogènes; IRM; Activité enzymatique; Molecular imaging; Chemical biology; Magnetogenic probes; Fluorogenic probes; Enzyme activity

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APA (6^th Edition):

Gondrand, C. (2016). Étude chémobiologique de sondes magnétogènes et fluorogènes pour l'imagerie moléculaire : Magnetogenic and fluorogenic probes for molecular imaging : a chemical biology study. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2016LYSEN070

Chicago Manual of Style (16^th Edition):

Gondrand, Corentin. “Étude chémobiologique de sondes magnétogènes et fluorogènes pour l'imagerie moléculaire : Magnetogenic and fluorogenic probes for molecular imaging : a chemical biology study.” 2016. Doctoral Dissertation, Lyon. Accessed January 15, 2021. http://www.theses.fr/2016LYSEN070.

MLA Handbook (7^th Edition):

Gondrand, Corentin. “Étude chémobiologique de sondes magnétogènes et fluorogènes pour l'imagerie moléculaire : Magnetogenic and fluorogenic probes for molecular imaging : a chemical biology study.” 2016. Web. 15 Jan 2021.

Vancouver:

Gondrand C. Étude chémobiologique de sondes magnétogènes et fluorogènes pour l'imagerie moléculaire : Magnetogenic and fluorogenic probes for molecular imaging : a chemical biology study. [Internet] [Doctoral dissertation]. Lyon; 2016. [cited 2021 Jan 15]. Available from: http://www.theses.fr/2016LYSEN070.

Council of Science Editors:

Gondrand C. Étude chémobiologique de sondes magnétogènes et fluorogènes pour l'imagerie moléculaire : Magnetogenic and fluorogenic probes for molecular imaging : a chemical biology study. [Doctoral Dissertation]. Lyon; 2016. Available from: http://www.theses.fr/2016LYSEN070

University of Illinois – Urbana-Champaign

18. Reinhardt, Christopher J. Chemical probes for studying cyclooxygenase-2 and nitric oxide in living systems.

Degree: PhD, Chemistry, 2020, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/108487

► Molecular imaging enables the direct detection of analytes and biomolecular species within their native biological environment. Although the field derives from diagnostic biomedical imaging, there… (more)

Subjects/Keywords: molecular imaging; reaction-based chemical probes; activity-based sensing; cyclooxygenase; nitric oxide; fluorescence imaging; photoacoustic imaging

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APA (6^th Edition):

Reinhardt, C. J. (2020). Chemical probes for studying cyclooxygenase-2 and nitric oxide in living systems. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/108487

Chicago Manual of Style (16^th Edition):

Reinhardt, Christopher J. “Chemical probes for studying cyclooxygenase-2 and nitric oxide in living systems.” 2020. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 15, 2021. http://hdl.handle.net/2142/108487.

MLA Handbook (7^th Edition):

Reinhardt, Christopher J. “Chemical probes for studying cyclooxygenase-2 and nitric oxide in living systems.” 2020. Web. 15 Jan 2021.

Vancouver:

Reinhardt CJ. Chemical probes for studying cyclooxygenase-2 and nitric oxide in living systems. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2020. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/2142/108487.

Council of Science Editors:

Reinhardt CJ. Chemical probes for studying cyclooxygenase-2 and nitric oxide in living systems. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2020. Available from: http://hdl.handle.net/2142/108487

University of California – San Diego

19. Cao, Kevin Jay. Development of Fluorescent Methods for the Detection of Amyloidosis in Neurodegeneration.

Degree: Chemistry, 2016, University of California – San Diego

URL: http://www.escholarship.org/uc/item/0m51k549

► At the molecular level, neurodegeneration is characterized by the appearance of aggregates of misfolded proteins known as amyloids. These assemblies are often associated with neurotoxicity… (more)

Subjects/Keywords: Chemistry; Neurosciences; Alzheimer's Disease; Amyloid detection; Creutzfeldt-Jakob's Disease; Fluorescent probes; Retinal imaging

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APA (6^th Edition):

Cao, K. J. (2016). Development of Fluorescent Methods for the Detection of Amyloidosis in Neurodegeneration. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/0m51k549

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cao, Kevin Jay. “Development of Fluorescent Methods for the Detection of Amyloidosis in Neurodegeneration.” 2016. Thesis, University of California – San Diego. Accessed January 15, 2021. http://www.escholarship.org/uc/item/0m51k549.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cao, Kevin Jay. “Development of Fluorescent Methods for the Detection of Amyloidosis in Neurodegeneration.” 2016. Web. 15 Jan 2021.

Vancouver:

Cao KJ. Development of Fluorescent Methods for the Detection of Amyloidosis in Neurodegeneration. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2021 Jan 15]. Available from: http://www.escholarship.org/uc/item/0m51k549.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cao KJ. Development of Fluorescent Methods for the Detection of Amyloidosis in Neurodegeneration. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/0m51k549

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas A&M University

20. Meenashi Sundaram, Vijay. Nanoscale Light Focusing and Imaging with Nano-Optical Devices.

Degree: PhD, Mechanical Engineering, 2014, Texas A&M University

URL: http://hdl.handle.net/1969.1/153896

► Energy transport analysis of micro/nano optics as well as their optimization to achieve high-throughput deep nanoscale patterning and microscopy is the goal of this study.… (more)

▼ Energy transport analysis of micro/nano optics as well as their optimization to achieve high-throughput deep nanoscale patterning and microscopy is the goal of this study. To understand the energy transport in nano-optical devices, the transient heating behavior of a commercial available nano-optical probe, NSOM, under pulsed laser operation is examined first. Based on the thermal analysis, it is observed that the major limitation of the NSOM probe under higher energy operation arises from the joule heating of its thin metal coating and the resulting thermal/mechanical damage during operation. Based on the understanding, a diffraction-based micro-zone plate (MZP) optical probe suffers less from joule heating and with advantages of higher optical throughput as well as longer working distance is designed and constructed. The MZP is fabricated at the end face of an optical fiber with a micro-fabrication technique based on e-beam negative tone lift-off lithography on non-planar substrates. The fabricated MZP can achieve spot sizes ~ 0.7λ at a focus distance of ~ 6λ with an optical transport efficiency of 20 %, which is more than 3 orders higher than that of NSOM. To further reduce the size of the focus spot to deep sub-wavelength scales and to eliminate metallic structures which can cause joule heating during high energy operation, two all-dielectric optical probes are then designed/constructed, namely, (a) solid immersion probe, and (b) scattering dielectric probe. Both dielectric probes focus light by combining more than one of the diffraction mechanisms associated with dielectric material (e.g., refraction, solid immersion, Mie and near-field Rayleigh scattering) to achieve deep nanoscale light focusing with minimum energy loss. The solid immersion optical probe is constructed with a ball lens and microsphere for macro to micro scale focusing with far field refraction and micro to mesocale focusing with solid immersion. The ball lens and the microsphere are stacked on an optical fiber for achieving the cascade focusing configuration. The solid immersion probe can achieve a focus spot size of ~ 0.45λ/n (~ 0.3λ when n = 1.5) on a target in the near field of the surface of the microsphere when the light is radially polarized. To achieve an even smaller focal spot in the near field, the scattering dielectric optical probe combines the verified solid immersion probe with a nano-scatterer at its focal spot. Due to the near-field Rayleigh scattering, the nano scatterer can induce a deep nanoscale spot with a diameter comparable to the forward radius of curvature of the scatterer under radially polarized light. It is verified with full wave electrodynamics simulations that the resulting scattering optical probe can achieve a ~10 nm spot with an intensity enhancement of ~ 10⁵, which can be valuable in all kinds of bio-detection as well as nano fabrications. At the end of the Ph.D study, mechanisms for deep sub-wavelength imaging resolutions with microspheres, which is recently demonstrated in different groups, are… Advisors/Committee Members: Wen, Sy-Bor (advisor), Suh, Steve (committee member), Yu, Choongho (committee member), Su, Chin B (committee member).

Subjects/Keywords: Nano-optic probes; NSOM; nanoscale light focusing; imaging; non-contact temperature measurement; theromoreflectance

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APA (6^th Edition):

Meenashi Sundaram, V. (2014). Nanoscale Light Focusing and Imaging with Nano-Optical Devices. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/153896

Chicago Manual of Style (16^th Edition):

Meenashi Sundaram, Vijay. “Nanoscale Light Focusing and Imaging with Nano-Optical Devices.” 2014. Doctoral Dissertation, Texas A&M University. Accessed January 15, 2021. http://hdl.handle.net/1969.1/153896.

MLA Handbook (7^th Edition):

Meenashi Sundaram, Vijay. “Nanoscale Light Focusing and Imaging with Nano-Optical Devices.” 2014. Web. 15 Jan 2021.

Vancouver:

Meenashi Sundaram V. Nanoscale Light Focusing and Imaging with Nano-Optical Devices. [Internet] [Doctoral dissertation]. Texas A&M University; 2014. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/1969.1/153896.

Council of Science Editors:

Meenashi Sundaram V. Nanoscale Light Focusing and Imaging with Nano-Optical Devices. [Doctoral Dissertation]. Texas A&M University; 2014. Available from: http://hdl.handle.net/1969.1/153896

University of California – Berkeley

21. Ramos Torres, Karla Michelle. Development of New Imaging Agents for the Study of Cellular Copper Dynamics.

Degree: Chemistry, 2016, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/17n1g7x7

► Copper is an essential element in biological systems. Its participation as a catalytic and structural cofactor in enzymes that function in biological processes such as… (more)

▼ Copper is an essential element in biological systems. Its participation as a catalytic and structural cofactor in enzymes that function in biological processes such as energy generation, oxygen transport, cellular metabolism and signal transduction renders it vital for the life of eukaryotic organisms. However, if misregulated, it can cause cellular oxidative damage through the production of highly reactive oxygen species. Consequently, it is not surprising that organisms have developed intricate cellular machineries to tightly regulate the trafficking of copper. The fascinating balance between the functional and pathological roles of copper has significantly motivated the study of the processes involved in the proper management of this metal in the cell by inspection of the total metal content in biological samples and its distribution into static and labile cellular pools. Traditional bulk techniques, in combination with biochemical and genetic methods, have been used probe the static copper pool and provide a general understanding of how cells handle copper ions, allowing for the identification of major proteins and ligands involved in copper homeostasis. Alternatively, molecular imaging provides a complementary, versatile approach that can be used to monitor dynamic fluxes of the labile copper pools in real time with spatial and temporal resolution. This dissertation describes the design, synthesis and characterization of new copper-responsive fluorescent sensors in order to expand the available toolbox for molecular imaging of copper dynamics. Application of a novel carbo-rhodol scaffold allowed for the development of the Copper CarboRhodol (CCR) and Copper CarboFluor (CCF) probes, that in combination with additional rhodol platforms extended the available color palette of copper-selective probes. Additionally, the design of unique metal binding motifs with altered ligand architectures, binding geometries and coordination units resulted in the synthesis of new copper-responsive fluorophores. Alteration of the coordination unit and inclusion of a tripodal ligand topology afforded a family of xanthene-based sensors with an assortment of fluorescent responses to copper and ability to sense fluctuations in endogenous, labile copper pools. Finally, development of a modified donor set that increases the number of available donors in the ligand framework was investigated as an alternative strategy to modulate the binding properties of the resulting copper sensors.

Subjects/Keywords: Chemistry; Inorganic chemistry; Organic chemistry; copper; fluorescent probes; ligand design; molecular imaging

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APA (6^th Edition):

Ramos Torres, K. M. (2016). Development of New Imaging Agents for the Study of Cellular Copper Dynamics. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/17n1g7x7

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ramos Torres, Karla Michelle. “Development of New Imaging Agents for the Study of Cellular Copper Dynamics.” 2016. Thesis, University of California – Berkeley. Accessed January 15, 2021. http://www.escholarship.org/uc/item/17n1g7x7.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ramos Torres, Karla Michelle. “Development of New Imaging Agents for the Study of Cellular Copper Dynamics.” 2016. Web. 15 Jan 2021.

Vancouver:

Ramos Torres KM. Development of New Imaging Agents for the Study of Cellular Copper Dynamics. [Internet] [Thesis]. University of California – Berkeley; 2016. [cited 2021 Jan 15]. Available from: http://www.escholarship.org/uc/item/17n1g7x7.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ramos Torres KM. Development of New Imaging Agents for the Study of Cellular Copper Dynamics. [Thesis]. University of California – Berkeley; 2016. Available from: http://www.escholarship.org/uc/item/17n1g7x7

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Notre Dame

22. Cynthia L. Spires. Near-Infrared Fluorescent Peptide Probes for Imaging Cancer</h1>.

Degree: Chemistry and Biochemistry, 2020, University of Notre Dame

URL: https://curate.nd.edu/show/bz60cv46s8g

► Cancer imaging is useful for multiple clinical and research purposes such as diagnostics, surgery guidance, monitoring disease progression, and metastasis detection. In particular, fluorescence… (more)

▼ Cancer imaging is useful for multiple clinical and research purposes such as diagnostics, surgery guidance, monitoring disease progression, and metastasis detection. In particular, fluorescence imaging has the advantage of being relatively non-toxic and inexpensive compared to other imaging modalities, and thus, there is a need to create new classes of cancer-targeted fluorescent probes. This thesis describes cancer imaging studies using novel molecular probes based on two near-infrared dyes called squaraine dyes and heptamethine cyanine dyes. The first half of Chapter 1 provides a broad introduction to the different strategies that are used to fabricate molecular probes. Over the last decade, covalent click chemistry has emerged as a powerful synthetic method for connecting two molecules together to make a larger conjugate for molecular imaging. Also discussed is the new concept of non-covalent click chemistry as an effective way to conjugate molecules rapidly and under mild conditions. The second half of Chapter 1 provides a broad introduction to the concept of targeted cancer imaging using targeted molecular probes. The focus is on aminopeptidase N as a molecular protein target that is overexpressed on the surface of cancer cells and tumor vasculature. Many different imaging modalities have been investigated in recent years and the work is presented as a classic example of systematic progress in modern molecular imaging. The second chapter describes an imaging study using a new squaraine fluorescent probe with a covalently attached cyclized peptide sequence Arg-Gly-Asp-D-Phe-Lys (cRGDfK). The cRGDfK peptide targets integrin receptors overexpressed on the surface of cancer cells and tumor vasculature. The probe was utilized to fluorescently image a clinically relevant mouse tumor model of ovarian cancer. In the second half of the chapter, the cRGDfK peptide was incorporated onto a tetralactam macrocycle which subsequently threaded a squaraine dye. The pre-assembled probe was used to successfully target implanted tumors comprised of non-small cell lung cancer cells. The third chapter summarizes a study using a new non-covalent cRGDfK probe with a different tetralactam macrocycle and squaraine dye. This probe permitted successful targeting of a cancerous tumor in a mouse model and enabled a mock surgery that removed the tumor. However, the tumor-to-background ratio varied significantly between mice due to tumor-to-tumor variability of the vasculature structure and interstitial pressure. Thus, a new paired agent imaging technique was developed where squaraine dyes with two different emission wavelengths were encapsulated within either a cRGDfK macrocycle or an untargeted macrocycle. The non-covalent probes were simultaneously injected into tumor-bearing mice and imaging showed enhanced tumor accumulation of the targeted probe with less tumor-to-tumor variability. The fourth chapter describes a new probe molecule whose structure is based on a figure-eight scaffold. The scaffold permits easy… Advisors/Committee Members: Paul W. Huber, Committee Member, Bradley D. Smith, Research Director, Mary S. Stack, Committee Member.

Subjects/Keywords: Fluorescence-guided surgery; Fluorescence imaging; Heptamethine cyanine dyes; Cancer targeted probes; Squaraine dyes

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APA (6^th Edition):

Spires, C. L. (2020). Near-Infrared Fluorescent Peptide Probes for Imaging Cancer</h1>. (Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/bz60cv46s8g

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Spires, Cynthia L.. “Near-Infrared Fluorescent Peptide Probes for Imaging Cancer</h1>.” 2020. Thesis, University of Notre Dame. Accessed January 15, 2021. https://curate.nd.edu/show/bz60cv46s8g.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Spires, Cynthia L.. “Near-Infrared Fluorescent Peptide Probes for Imaging Cancer</h1>.” 2020. Web. 15 Jan 2021.

Vancouver:

Spires CL. Near-Infrared Fluorescent Peptide Probes for Imaging Cancer</h1>. [Internet] [Thesis]. University of Notre Dame; 2020. [cited 2021 Jan 15]. Available from: https://curate.nd.edu/show/bz60cv46s8g.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Spires CL. Near-Infrared Fluorescent Peptide Probes for Imaging Cancer</h1>. [Thesis]. University of Notre Dame; 2020. Available from: https://curate.nd.edu/show/bz60cv46s8g

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Michigan Technological University

23. Fang, Mingxi. NOVEL FLUORESCENT PROBES FOR VISUALIZATION OF pH CHANGES AND Zn (Ⅱ) IONS IN LIVE CELLS.

Degree: PhD, Department of Chemistry, 2018, Michigan Technological University

URL: https://digitalcommons.mtu.edu/etdr/726

► Intracellular pH plays many significant roles in various cellular processes including cell proliferation, cell growth, apoptosis, signal transduction, and cellular metabolism. Lysosome is a… (more)

▼ Intracellular pH plays many significant roles in various cellular processes including cell proliferation, cell growth, apoptosis, signal transduction, and cellular metabolism. Lysosome is a membrane-bound organelle with pH 4.5-5.0 which is found in virtually all animal cells. Zn (II) ions extensively exist in human cells and body fluid. Research revealed that Zn (II) ions involved in many metabolism process such as cell growth, reproduction, and tissue regeneration. Near-infrared (NIR) fluorescent probes for the detection of intracellular pH and Zn (II) ions have become hot research topics because of the advantages of high sensitivity, easy operation, deep tissues penetration, real-time monitoring, and low background interference. In this dissertation, we reported two NIR fluorescent probes for sensing of intracellular Zn (II) ions. The probes show advantages of large Stokes shift, excellent photostability and good selectivity to Zn (II) over other metal ions. We also developed five coumarin-hybridized near-infrared fluorescent probes for sensing of lysosomal pH changes in both NIR and visible regions. We significantly improved compatibility and water-solubility of the probes by introducing oligo(ethylene glycol) to the fluorophores. In order to overcome fluorescence quenching issue of cyanine dye (IR-780) in aqueous solution, we successfully developed a fluorescent cassette by introducing tetraphenylethene (TPE) derivative to dye IR-780 through an ether bond connection. Both TPE donor and cyanine acceptor in the cassette show significant fluorescence enhancement when the fluorescent cassette becomes aggregated in aqueous solutions. The fluorescent cassette has been used to detect intracellular pH changes in live cells through manipulation of the cassette aggregation status by pH changes. In order to overcome systematic errors of intensity-based fluorescent probes, we also developed three ratiometric fluorescent probes based on BODIPY donors and near-infrared rhodamine or hemicyanine acceptors through electric wire pi-conjugation connections in a through-bond energy transfer approach The probes display ratiometric fluorescence responses to pH decreases from 7.4 to 2.4 with fluorescence decreases of BODIPY donors and fluorescence increases of rhodamine or hemicyanine acceptors. Advisors/Committee Members: Haiying Liu.

Subjects/Keywords: fluorescent probes; pH; Zn (Ⅱ) ions; cell imaging; Analytical Chemistry; Biochemistry; Organic Chemicals; Organic Chemistry

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APA (6^th Edition):

Fang, M. (2018). NOVEL FLUORESCENT PROBES FOR VISUALIZATION OF pH CHANGES AND Zn (Ⅱ) IONS IN LIVE CELLS. (Doctoral Dissertation). Michigan Technological University. Retrieved from https://digitalcommons.mtu.edu/etdr/726

Chicago Manual of Style (16^th Edition):

Fang, Mingxi. “NOVEL FLUORESCENT PROBES FOR VISUALIZATION OF pH CHANGES AND Zn (Ⅱ) IONS IN LIVE CELLS.” 2018. Doctoral Dissertation, Michigan Technological University. Accessed January 15, 2021. https://digitalcommons.mtu.edu/etdr/726.

MLA Handbook (7^th Edition):

Fang, Mingxi. “NOVEL FLUORESCENT PROBES FOR VISUALIZATION OF pH CHANGES AND Zn (Ⅱ) IONS IN LIVE CELLS.” 2018. Web. 15 Jan 2021.

Vancouver:

Fang M. NOVEL FLUORESCENT PROBES FOR VISUALIZATION OF pH CHANGES AND Zn (Ⅱ) IONS IN LIVE CELLS. [Internet] [Doctoral dissertation]. Michigan Technological University; 2018. [cited 2021 Jan 15]. Available from: https://digitalcommons.mtu.edu/etdr/726.

Council of Science Editors:

Fang M. NOVEL FLUORESCENT PROBES FOR VISUALIZATION OF pH CHANGES AND Zn (Ⅱ) IONS IN LIVE CELLS. [Doctoral Dissertation]. Michigan Technological University; 2018. Available from: https://digitalcommons.mtu.edu/etdr/726

24. Li, Chenge. Development of bioorthogonal fluorogenic reporters for biological imaging : Développement de marqueurs fluorogéniques bioorthogonaux pour l'imagerie biologique.

Degree: Docteur es, Chimie physique, 2017, Paris Sciences et Lettres (ComUE)

URL: http://www.theses.fr/2017PSLEE044

►

L'étude de la dynamique des protéines est essentielle pour comprendre les processus biologiques. Notre laboratoire a développé une nouvelle classe de protéines fluorescentes semi-synthétiques, appelée… (more)

▼

L'étude de la dynamique des protéines est essentielle pour comprendre les processus biologiques. Notre laboratoire a développé une nouvelle classe de protéines fluorescentes semi-synthétiques, appelée Fluorescence-Activating and absorption-Shifting Tag (FAST). Cette thèse de doctorat présente le développement de nouveaux systèmes FAST avec diverses propriétés pour l'imagerie multiplexée. Nous avons développé une série de fluorogènes permettant de modifier la couleur de FAST de vert-jaune à orange et rouge. Au delà de l’application de l’imagerie multi-couleurs, ces fluorogènes permettant un échange dynamique des couleurs grâce à la liaison réversible de FAST, ouvrant de nouvelles perspectives pour le développement de méthodes d’imagerie sélective reposant sur la dynamique de systèmes réactifs. Pour étendre davantage les propriétés spectrales de FAST vers le rouge lointain, nous avons développé une nouvelle série de fluorogènes rouges, pour lesquels nous avons sélectionné par une stratégie d'évolution dirigée basée sur le yeast display et la cytométrie en flux de nouveaux tags protéiques capables d’interagir avec ces fluorogènes et d’activer leur fluorescence. Nous avons enfin développé de nouveaux fluorogènes capables de former des complexes fluorescents avec FAST, mais incapables de traverser la membrane plasmique, ce qui permet de détecter sélectivement les protéines membranaires.

Studying protein activities could help us to understand the complex mechanisms controlling cells and organisms. Our laboratory recently developed Fluorescence-Activating and absorption-Shifting Tag (FAST), a small fluorogen-based reporter enabling to fluorescently label fusion proteins in living cells. My PhD thesis presents the developments of new FAST systems with various properties for multiplexed imaging. We report a collection of fluorogens enabling to tune the fluorescence color of FAST from green-yellow to orange and red. Beyond allowing multicolor imaging of FAST-tagged proteins in live cells, these fluorogens enable dynamic color switching because of FAST’s reversible labeling, opening great prospects for the design of selective imaging methods relying on dynamic systems. In order to further expand the spectral properties of FAST to red, we also designed and developed a library of red fluorogenic dyes, for which we engineered specific protein binders by applying a directed evolution strategy based on the yeast display technology and high-throughput fluorescence activating cell sorting (FACS). We finally developed novel fluorogens able to form fluorescent complexes with FAST, but incapable of crossing the plasma membrane, which makes it possible to selectively detect FAST-tagged cell-surface proteins.

Advisors/Committee Members: Gautier, Arnaud (thesis director).

Subjects/Keywords: Marqueur fluorogénique,; Fluorescence; Marquage protéique; Imagerie biologique; Fluorogenic probes; Fluorescence; Protein labeling; Biological imaging; 541.3

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APA (6^th Edition):

Li, C. (2017). Development of bioorthogonal fluorogenic reporters for biological imaging : Développement de marqueurs fluorogéniques bioorthogonaux pour l'imagerie biologique. (Doctoral Dissertation). Paris Sciences et Lettres (ComUE). Retrieved from http://www.theses.fr/2017PSLEE044

Chicago Manual of Style (16^th Edition):

Li, Chenge. “Development of bioorthogonal fluorogenic reporters for biological imaging : Développement de marqueurs fluorogéniques bioorthogonaux pour l'imagerie biologique.” 2017. Doctoral Dissertation, Paris Sciences et Lettres (ComUE). Accessed January 15, 2021. http://www.theses.fr/2017PSLEE044.

MLA Handbook (7^th Edition):

Li, Chenge. “Development of bioorthogonal fluorogenic reporters for biological imaging : Développement de marqueurs fluorogéniques bioorthogonaux pour l'imagerie biologique.” 2017. Web. 15 Jan 2021.

Vancouver:

Li C. Development of bioorthogonal fluorogenic reporters for biological imaging : Développement de marqueurs fluorogéniques bioorthogonaux pour l'imagerie biologique. [Internet] [Doctoral dissertation]. Paris Sciences et Lettres (ComUE); 2017. [cited 2021 Jan 15]. Available from: http://www.theses.fr/2017PSLEE044.

Council of Science Editors:

Li C. Development of bioorthogonal fluorogenic reporters for biological imaging : Développement de marqueurs fluorogéniques bioorthogonaux pour l'imagerie biologique. [Doctoral Dissertation]. Paris Sciences et Lettres (ComUE); 2017. Available from: http://www.theses.fr/2017PSLEE044

25. Love, Brian William. Synthesis and characterization of time-resolved lanthanide (III) luminescent probes for potential detection of melanoma skin cancer.

Degree: 2017, NC Docks

URL: http://libres.uncg.edu/ir/wcu/f/Love2017.pdf

► The focal point of this research is to continue the development of a time-resolved lanthanide (III) luminescent probe that may aid in early detection of… (more)

Subjects/Keywords: Luminescent probes; Rare earth metals – Optical properties; Melanoma – Early detection; Biosensors; Imaging systems in biology

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APA (6^th Edition):

Love, B. W. (2017). Synthesis and characterization of time-resolved lanthanide (III) luminescent probes for potential detection of melanoma skin cancer. (Thesis). NC Docks. Retrieved from http://libres.uncg.edu/ir/wcu/f/Love2017.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Love, Brian William. “Synthesis and characterization of time-resolved lanthanide (III) luminescent probes for potential detection of melanoma skin cancer.” 2017. Thesis, NC Docks. Accessed January 15, 2021. http://libres.uncg.edu/ir/wcu/f/Love2017.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Love, Brian William. “Synthesis and characterization of time-resolved lanthanide (III) luminescent probes for potential detection of melanoma skin cancer.” 2017. Web. 15 Jan 2021.

Vancouver:

Love BW. Synthesis and characterization of time-resolved lanthanide (III) luminescent probes for potential detection of melanoma skin cancer. [Internet] [Thesis]. NC Docks; 2017. [cited 2021 Jan 15]. Available from: http://libres.uncg.edu/ir/wcu/f/Love2017.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Love BW. Synthesis and characterization of time-resolved lanthanide (III) luminescent probes for potential detection of melanoma skin cancer. [Thesis]. NC Docks; 2017. Available from: http://libres.uncg.edu/ir/wcu/f/Love2017.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Portland State University

26. Munhenzva, Ian Ruramai. Optimized Xanthene-based Probes for Pancreatic Cancer Imaging.

Degree: PhD, Chemistry, 2020, Portland State University

URL: https://pdxscholar.library.pdx.edu/open_access_etds/5461

► Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest human malignancies with an extremely poor 5-year survival rate of below 5%. Surgical resection is… (more)

▼ Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest human malignancies with an extremely poor 5-year survival rate of below 5%. Surgical resection is the most effective treatment of choice because chemotherapy and radiation therapy do not improve life expectancy. Residual tumor after PDAC surgery is common due to a lack of PDAC targeted intraoperative contrast agents to confirm clear margins. Fluorescence imaging has the potential to improve surgery outcome and PDAC patients' survival rate via the use of highly PDAC-specific molecular probes to facilitate tumor identification. This thesis describes the application of a focused library of benzoxanthene fluorophores for PDAC margin assessment. This work shows the utility of fluorophore 12 in the ex vivo staining of human PDAC tissue. When 12 was used for ex vivo staining of healthy pancreas and PDAC tissue, it displayed visually higher localization in the PDAC-associated ductal epithelial cells compared to the healthy tissue. We optimized the ex vivo staining conditions such as fluorophore concentration, fluorophore incubation and washing time, for clinical translation. A receiver operator characteristic (ROC) curve analysis was used as a non-subjective evaluation for effective contrast between cancer and healthy tissue, confirming high throughput and efficient screening for the investigated parameters. The need for dyes that are active in the near-infrared region (NIR) region (>700 nm) and have large Stoke shifts led to the design and synthesis of a benzo[a]xanthene library. Among other advantages, imaging in the NIR results in reduced tissue damage and reduced photobleaching of the fluorophore. The benzo[a]xanthene library shows at least two-fold enhanced brightness compared to the benzo[c]xanthene library, along with no significant bathochromic shift, as predicted by density functional theory (DFT) calculations. Compound 8, a regioisomer of 12 with analogous physicochemical properties, showed selectivity for PDAC but was not as optimal as 12. The functionalization of the benzo[c]xanthene chromophore with a cyanine chromophore moiety was proposed towards developing NIR-active fluorophores. The synthesis of cyanine-xanthene hybrids was begun. Once the synthesis is optimized, the hybrid dyes will be screened for PDAC selectivity and subsequently used for PDAC margin assessment. Advisors/Committee Members: Robert M. Strongin.

Subjects/Keywords: Fluorescent probes – Diagnostic use; Xanthene dyes; Pancreas – Tumors – Identification; Pancreas – Cancer – Imaging; Pancreas – Cancer – Spectroscopic imaging; Biomedical Engineering and Bioengineering; Chemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Munhenzva, I. R. (2020). Optimized Xanthene-based Probes for Pancreatic Cancer Imaging. (Doctoral Dissertation). Portland State University. Retrieved from https://pdxscholar.library.pdx.edu/open_access_etds/5461

Chicago Manual of Style (16^th Edition):

Munhenzva, Ian Ruramai. “Optimized Xanthene-based Probes for Pancreatic Cancer Imaging.” 2020. Doctoral Dissertation, Portland State University. Accessed January 15, 2021. https://pdxscholar.library.pdx.edu/open_access_etds/5461.

MLA Handbook (7^th Edition):

Munhenzva, Ian Ruramai. “Optimized Xanthene-based Probes for Pancreatic Cancer Imaging.” 2020. Web. 15 Jan 2021.

Vancouver:

Munhenzva IR. Optimized Xanthene-based Probes for Pancreatic Cancer Imaging. [Internet] [Doctoral dissertation]. Portland State University; 2020. [cited 2021 Jan 15]. Available from: https://pdxscholar.library.pdx.edu/open_access_etds/5461.

Council of Science Editors:

Munhenzva IR. Optimized Xanthene-based Probes for Pancreatic Cancer Imaging. [Doctoral Dissertation]. Portland State University; 2020. Available from: https://pdxscholar.library.pdx.edu/open_access_etds/5461

University of Saskatchewan

27. Nwabufo, Chukwunonso Kingsley 1991-. Preclinical Development of Novel Bifunctional Compounds for Parkinson's Disease.

Degree: 2019, University of Saskatchewan

URL: http://hdl.handle.net/10388/11896

► The development of disease-modifying drugs and differential diagnostic agents is a current focus of research in Parkinson’s disease (PD) and one putative target is alpha-synuclein… (more)

▼ The development of disease-modifying drugs and differential diagnostic agents is a current focus of research in Parkinson’s disease (PD) and one putative target is alpha-synuclein (AS). Recently, we reported that two bifunctional compounds composed of a caffeine scaffold attached to nicotine (C(8)-6-N) and 1-aminoindan (C(8)-6-I) could prevent AS mediated toxicity in a yeast model of PD. Although caffeine linked to caffeine (C(8)-6-C(8)) did not show any therapeutic potentials, it demonstrated the strongest binding to AS. To better understand the biodistribution of C(8)-6-I, C(8)-6-N, and C(8)-6-C(8) in vivo we are developing methods to label the bifunctional compounds with Fluorine-18 (18F) to use in positron emission tomography (PET) imaging studies. Given the therapeutic and diagnostic potentials of these bifunctional compounds, it is necessary to conduct further preclinical studies to understand their safety and efficacy. The overall goal of this study is to establish the tandem mass spectrometric fingerprints of the target compounds which can help in metabolite identification and for the development of qualitative and quantitative methods. Also, the metabolic profile for C(8)-6-I, C(8)-6-N, and C(8)-6-C(8) in human, mouse, and rat liver microsomes (HLM, MLM, and RLM) were evaluated. Tandem mass spectrometric studies were performed using hybrid quadrupole-time of flight and triple quadrupole-linear ion trap mass spectrometers. Metabolite profiling was accomplished using accurate mass measurement and tandem mass spectrometry. A significant observation in the fragmentation of C(8)-6-C(8) suggests that a previously reported loss of acetaldehyde during caffeine fragmentation is instead a loss of carbon dioxide. While the caffeine scaffold in C(8)-6-N, C(8)-6-I, and C(8)-6-C(8) was metabolically stable, the nicotine and 1-aminoindan moieties were either cleaved off (dealkylation) or hydroxylated in HLM, MLM and RLM indicating that the caffeine moiety may be the preferable spot for the inclusion of 18F radioisotope in these bifunctional compounds. Given the similarity in the metabolic pathways, mouse and rat may be useful surrogates for future animal studies of C(8)-6-I, C(8)-6-N, and C(8)-6-C(8). Advisors/Committee Members: Krol, Edward, El-Aneed, Anas, Katselis, George, Dadachova, Kate.

Subjects/Keywords: Parkinson's disease; alpha-synuclein; drug metabolism; tandem mass spectrometry; bifunctional compounds; positron emission tomography imaging probes; disease-modifying drugs; differential diagnostic probes; new chemical entities; liver microsomes

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APA (6^th Edition):

Nwabufo, C. K. 1. (2019). Preclinical Development of Novel Bifunctional Compounds for Parkinson's Disease. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/11896

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nwabufo, Chukwunonso Kingsley 1991-. “Preclinical Development of Novel Bifunctional Compounds for Parkinson's Disease.” 2019. Thesis, University of Saskatchewan. Accessed January 15, 2021. http://hdl.handle.net/10388/11896.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nwabufo, Chukwunonso Kingsley 1991-. “Preclinical Development of Novel Bifunctional Compounds for Parkinson's Disease.” 2019. Web. 15 Jan 2021.

Vancouver:

Nwabufo CK1. Preclinical Development of Novel Bifunctional Compounds for Parkinson's Disease. [Internet] [Thesis]. University of Saskatchewan; 2019. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/10388/11896.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nwabufo CK1. Preclinical Development of Novel Bifunctional Compounds for Parkinson's Disease. [Thesis]. University of Saskatchewan; 2019. Available from: http://hdl.handle.net/10388/11896

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. ElGamal, Mahmoud. Preparation and Evaluation of Molecular Imaging Probes for Breast Cancer.

Degree: MSc, 2014, McMaster University

URL: http://hdl.handle.net/11375/16037

►

Breast cancer remains the most commonly diagnosed cancer among women over the age of 20, as recently reported by the Canadian Cancer Society. Studies have… (more)

▼

Breast cancer remains the most commonly diagnosed cancer among women over the age of 20, as recently reported by the Canadian Cancer Society. Studies have shown a strong correlation between early detection and increased survival rates thus it is important to have a means to adequately screen and detect breast cancer. Currently, tests are limited to traditional imaging methods such as ultrasound (US), magnetic resonance imaging (MRI) and standard mammography. There remains a need for a molecular imaging probe that is capable of providing further prognostic information particularly with respect to assessing tumour aggressiveness and the likelihood of a cancer to metastasize. Overexpression of the insulin receptor (IR) has been detailed in patients with breast cancer but there is currently no means of non-invasive and quantifiable detection of the receptor. The goal of the work described here was to prepare an insulin derived nuclear imaging probe via direct coupling of a prosthetic group bearing a radionuclide to the B29 lysine (B29-Lys) residue of the hormone. Benzoic acid bearing halogens were chosen as model compounds. The lead candidate N-[4-fluorobenzoyl]-(B29-Lys) insulin (4) was prepared in 60% overall yield and showed affinity for the IR similar to that of native insulin (IC50=3.6 nM). The 18F analogue (9) was successfully synthesized and showed high stability (up to 4 hours) post formulation in both saline and phosphate buffered solution (PBS). The product represents a promising new probe for assessing the role of the IR in cancer growth and metastasis. A complementary strategy for imaging markers of tumour aggressiveness was investigated through the development of a novel ultrasound probe. A pretargeting approach involving urokinase plasminogen activator receptor (uPAR), which is known to play a role in cancer metastasis, was used to develop the agent of interest. Here an in vivo reaction between tetrazine tagged microbubbles (MBs) and anti-uPAR antibodies conjugated to trans-cyclooctene (TCO) was employed. Following preparation of the antibody conjugate and tetrazine functionalized MBs, preliminary in vitro testing in a flow cell system was conducted. Results showed the ability of the uPAR expressing cells to exclusively capture the tetrazine MBs after they have been previously incubated with the TCO anti-uPAR antibody. No capture was observed when the target and/or the antibody were absent. The contrast agent developed represents the first MB targeted against uPAR and has the potential to impact current diagnostic paradigms particularly given the widespread use of ultrasound in cancer patient management.

Thesis

Master of Science (MSc)

Advisors/Committee Members: Valliant, John F., Chemical Biology.

Subjects/Keywords: Imaging Probes; Breast Cancer; Insuin; uPAR

…validation of novel molecular imaging probes is an emerging area in cancer research. Figure 1… …used extensively to develop new molecular imaging probes. One example of a peptide that has… …retention at the target of interest.33 1.8.Insulin based nuclear imaging probes Many attempts to… …51 4.3. US Imaging… …54 4.4. Contrast Enhanced US Imaging Using Targeted Microbubbles (MB)…

11 more images…

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APA (6^th Edition):

ElGamal, M. (2014). Preparation and Evaluation of Molecular Imaging Probes for Breast Cancer. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/16037

Chicago Manual of Style (16^th Edition):

ElGamal, Mahmoud. “Preparation and Evaluation of Molecular Imaging Probes for Breast Cancer.” 2014. Masters Thesis, McMaster University. Accessed January 15, 2021. http://hdl.handle.net/11375/16037.

MLA Handbook (7^th Edition):

ElGamal, Mahmoud. “Preparation and Evaluation of Molecular Imaging Probes for Breast Cancer.” 2014. Web. 15 Jan 2021.

Vancouver:

ElGamal M. Preparation and Evaluation of Molecular Imaging Probes for Breast Cancer. [Internet] [Masters thesis]. McMaster University; 2014. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/11375/16037.

Council of Science Editors:

ElGamal M. Preparation and Evaluation of Molecular Imaging Probes for Breast Cancer. [Masters Thesis]. McMaster University; 2014. Available from: http://hdl.handle.net/11375/16037

29. Thörn Seshold, Oliver. Development of Auto-Immolative Spacers for Probes of Enzyme Activity : Développement d’espaceurs auto-effondrables pour des sondes d’activité enzymatique.

Degree: Docteur es, Chimie, 2013, Lyon, École normale supérieure

URL: http://www.theses.fr/2013ENSL0817

►

Cette thèse traite de la conception et mise en œuvre d’espaceurs auto-effondrables novateurs pour une utilisation dans des sondes d’activité enzymatique in vivo.La première partie… (more)

▼

Cette thèse traite de la conception et mise en œuvre d’espaceurs auto-effondrables novateurs pour une utilisation dans des sondes d’activité enzymatique in vivo.La première partie détaille la synthèse et la validation in vitro d’espaceurs cyclisant, couplant l’activité d’un aminopeptidase à la libération d’un phénol. Les sondes fluorogènes modulaires basées sur ces espaceurs 1,2-diamine sont très robustes (demi-vie > 560 h), mais sont rapidement enzymatiquement hydrolysées, et puis relâchent rapidement (demi-temps ~ 3 min) un fluorophore ESIPT insoluble et exceptionnellement photostable.Ces sondes ont une excellente sensibilité (rapport signal:contrôle > 3000:1), et fournissent la première démonstration d’un système macroscopiquement binaire éteint–ALLUMÉ, pour la libération de phénols sous activité d’aminopeptidases. Ce système pourrait permettre de faire de l’imagerie moléculaire ultra-sensible d’une gamme d’exopeptidases. Ces espaceurs pourraient également servir dans des sondes comportant d’autres fluorophores phénoliques, dans des promédicaments de phénols/alcools activés par des peptidases spécifiques (thérapies ciblées), ou comme adaptateurs chimiques en générale.La deuxième partie détaille les synthèses de deux familles d’espaceurs tautomérisant/éliminant pour utilisation dans des sondes magnétogènes d’activité de glycosidases. Les premières architectures substrat-espaceur basées sur des 2-furanols et des carbimidates cycliques ont été explorées. Notamment, des glycosides 2-furanoliques ont été abordés comme espaceurs énergétiques alternatifs aux quinone méthydes, et des carbimidates ont été explorés comme espaceurs pour ligands modèles des sondes promagnétiques.

This thesis concerns the design and implementation of novel auto-immolative spacers for use in probes for enzymatic activity in vivo.The first part relates the development and in vitro validation of cyclisation spacers which couple the action of an aminopeptidase to the release of a phenol. The modular three-component fluorogenic probes based on these 1,2-diamine spacers are very robust (halflife > 560 h), but are also rapidly enzymatically processed, and quickly (halftime ~3 min) release an exceptionally photostable, insoluble ESIPT fluorophore. The probes have excellent detection sensitivity relative to current methods (signal to control ratio > 3000:1), and provide the first demonstration of a macroscopically binary off–ON system for phenol-releasing probes of aminopeptidase activity. The probe system may allow the exceptionally sensitive, ESIPT-based molecular imaging of a range of exopeptidases. The spacers may also be applied in off ON peptidase probes of other phenolic fluorophores, to peptidase-specific phenol/alcohol prodrugs for targeted therapy, or more generally in chemical adapter technologies.In the second part, two novel families of auto-immolative elimination/tautomerisation spacers were designed for use in three-component off ON magnetogenic probes sensing glycosidase activity. The first known substrate-spacer designs based on…

Advisors/Committee Members: Hasserodt, Jens (thesis director).

Subjects/Keywords: Espaceurs auto-effondrables; Sondes moléculaires; Exopeptidases; Glycosidases; Agents d’imagerie; Auto-immolative spacers; Molecular probes; Exopeptidases; Glycosidases; Imaging agents

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APA (6^th Edition):

Thörn Seshold, O. (2013). Development of Auto-Immolative Spacers for Probes of Enzyme Activity : Développement d’espaceurs auto-effondrables pour des sondes d’activité enzymatique. (Doctoral Dissertation). Lyon, École normale supérieure. Retrieved from http://www.theses.fr/2013ENSL0817

Chicago Manual of Style (16^th Edition):

Thörn Seshold, Oliver. “Development of Auto-Immolative Spacers for Probes of Enzyme Activity : Développement d’espaceurs auto-effondrables pour des sondes d’activité enzymatique.” 2013. Doctoral Dissertation, Lyon, École normale supérieure. Accessed January 15, 2021. http://www.theses.fr/2013ENSL0817.

MLA Handbook (7^th Edition):

Thörn Seshold, Oliver. “Development of Auto-Immolative Spacers for Probes of Enzyme Activity : Développement d’espaceurs auto-effondrables pour des sondes d’activité enzymatique.” 2013. Web. 15 Jan 2021.

Vancouver:

Thörn Seshold O. Development of Auto-Immolative Spacers for Probes of Enzyme Activity : Développement d’espaceurs auto-effondrables pour des sondes d’activité enzymatique. [Internet] [Doctoral dissertation]. Lyon, École normale supérieure; 2013. [cited 2021 Jan 15]. Available from: http://www.theses.fr/2013ENSL0817.

Council of Science Editors:

Thörn Seshold O. Development of Auto-Immolative Spacers for Probes of Enzyme Activity : Développement d’espaceurs auto-effondrables pour des sondes d’activité enzymatique. [Doctoral Dissertation]. Lyon, École normale supérieure; 2013. Available from: http://www.theses.fr/2013ENSL0817

30. Bordy, Mathieu. Synthèse et évaluation biologique de sondes fluorogènes pour la détection d’activités enzymatiques : Synthesis and biological evaluation of fluorogenic probes for the detection of enzymatic activities.

Degree: Docteur es, Chimie, 2019, Lyon

URL: http://www.theses.fr/2019LYSEN072

►

Cette thèse de doctorat traite de la conception et de l’évaluation de sondes fluorogènes pour la détection d’activités enzymatiques dans des contextes biologiques d’intérêt. L’élaboration… (more)

▼

Cette thèse de doctorat traite de la conception et de l’évaluation de sondes fluorogènes pour la détection d’activités enzymatiques dans des contextes biologiques d’intérêt. L’élaboration de sondes fluorogéniques stables incorporant l’ELF-97 est une des thématiques de recherche activement poursuivie par notre équipe. Le développement avec succès de sondes peptidases et glycosidases a ouvert de nombreuses perspectives. Un premier chapitre sera dédié à la diversification de ces sondes, tout d’abord par la variation de substrats pour la détection de nouvelles glycosidases, puis par le développement d’un espaceur innovant dans un contexte particulier de sénescence cellulaire. Une sonde pour la détection de la β-galactosidase en milieu acide a notamment pu être synthétisée et testée. En parallèle, des travaux ont porté sur une nouvelle génération de sondes ciblant une famille d’enzymes à fort intérêt scientifique et sociétal : les β-lactamases. La synthèse et l’évaluation biologique préliminaire d’une première sonde modèle a démontré l’efficacité de cette nouvelle architecture moléculaire. Cette sonde a, par la suite, permis l’élaboration de premiers résultats d’imagerie dans le cadre d’une collaboration active avec une équipe de recherche japonaise. Enfin, un dernier volet sera consacré à un projet dont l’objectif n’est pas récent dans l’équipe : le développement d’alternatives à l’ELF-97 présentant une émission décalée vers le rouge ou le proche infrarouge. Ainsi, la synthèse de nouveaux fluorophores, leurs caractérisations physico-chimiques et des tests d’incorporation dans des dispositifs répondeurs ont notamment été réalisés. Plusieurs candidats se sont révélés à fort potentiel pour leur émission fortement décalée vers le rouge ou leur haute insolubilité. Ils pourraient permettre à terme l’adaptation de la technologie à une utilisation in vivo, but ultime de la technologie dans le cadre de l’imagerie moléculaire.

This doctoral thesis deals with the design and evaluation of fluorogenic probes for the detection of enzymatic activities in biological contexts of interest.The development of stable fluorogenic probes incorporating ELF-97 is one of the research themes actively pursued by our team. The successful development of peptidases and glycosidases probes have opened many perspectives. A first chapter will be dedicated to the diversification of these probes, firstly by the variation of substrates for the detection of new glycosidases, then by the development of an innovative spacer in the context of cell senescence. In particular, a probe for the detection of β-galactosidase in acidic medium has been synthesized and tested.In parallel, work has focused on a new generation of probes targeting an enzyme family with strong scientific and societal interest : β-lactamases. The synthesis and the preliminary biological evaluation of a first model probe demonstrated the effectiveness of this new molecular architecture. This probe subsequently led to the development of first imaging results as part of an active…

Advisors/Committee Members: Hasserodt, Jens (thesis director).

Subjects/Keywords: Imagerie moléculaire; Sondes fluorogènes; Activité enzymatique; Fluorescence proche-infrarouge; Molecular imaging; Fluorogenic probes; Enzymatic activity; Near-infrared fluorescence

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APA (6^th Edition):

Bordy, M. (2019). Synthèse et évaluation biologique de sondes fluorogènes pour la détection d’activités enzymatiques : Synthesis and biological evaluation of fluorogenic probes for the detection of enzymatic activities. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2019LYSEN072

Chicago Manual of Style (16^th Edition):

Bordy, Mathieu. “Synthèse et évaluation biologique de sondes fluorogènes pour la détection d’activités enzymatiques : Synthesis and biological evaluation of fluorogenic probes for the detection of enzymatic activities.” 2019. Doctoral Dissertation, Lyon. Accessed January 15, 2021. http://www.theses.fr/2019LYSEN072.

MLA Handbook (7^th Edition):

Bordy, Mathieu. “Synthèse et évaluation biologique de sondes fluorogènes pour la détection d’activités enzymatiques : Synthesis and biological evaluation of fluorogenic probes for the detection of enzymatic activities.” 2019. Web. 15 Jan 2021.

Vancouver:

Bordy M. Synthèse et évaluation biologique de sondes fluorogènes pour la détection d’activités enzymatiques : Synthesis and biological evaluation of fluorogenic probes for the detection of enzymatic activities. [Internet] [Doctoral dissertation]. Lyon; 2019. [cited 2021 Jan 15]. Available from: http://www.theses.fr/2019LYSEN072.

Council of Science Editors:

Bordy M. Synthèse et évaluation biologique de sondes fluorogènes pour la détection d’activités enzymatiques : Synthesis and biological evaluation of fluorogenic probes for the detection of enzymatic activities. [Doctoral Dissertation]. Lyon; 2019. Available from: http://www.theses.fr/2019LYSEN072

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Open Access Theses and Dissertations