You searched for subject:(Molecular imaging).
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Ryerson University
1.
Hussein, Farah.
On the molecular release induced by ultrasound and microbubbles in cells.
Degree: 2014, Ryerson University
URL: https://digital.library.ryerson.ca/islandora/object/RULA%3A3414 
► Ultrasound and microbubble (USMB) enhances intracellular uptake through membrane disruption and endocytosis. This study investigates USMB effects on the molecular release incells through membrane-disruption and…
(more)
▼ Ultrasound and microbubble (USMB) enhances intracellular uptake through membrane disruption and endocytosis. This study investigates USMB effects on the
molecular release incells through membrane-disruption and exocytosis. Retinal pigmented epithelial (RPE) cells were loaded with Alexa 647-transferrin (Tfn) to mark recycling endosomes, LAMP-1
antibody was used to mark lysosomes, GFP-transfected RPE cells were used to mark cytoplasm, and 7-AAD was used to assess cell viability. USMB exposure was done at 570kPa peak negative pressure for 1min. The mean fluorescent intensities (MFI) of markers were measured using flow cytometry. USMB induced the release of 19% and 67% of GFP from the cytoplasm in viable and non-viable cells respectively. LAMP-1 antibody MFI increased by 50% and 15-folds in viable and non-viable cells indicating USMB induced release from lysosomes. Furthermore, Tfn release from recycling endosomes increased by 22% only in viable cells. In conclusion, USMB enhances the
molecular release from cytoplasm, lysosomes, and recycling endosomes
Advisors/Committee Members: Ryerson University (Degree grantor).
Subjects/Keywords: Cytology; Ultrasonic imaging; Molecular neurobiology
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APA (6th Edition):
Hussein, F. (2014). On the molecular release induced by ultrasound and microbubbles in cells. (Thesis). Ryerson University. Retrieved from https://digital.library.ryerson.ca/islandora/object/RULA%3A3414
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hussein, Farah. “On the molecular release induced by ultrasound and microbubbles in cells.” 2014. Thesis, Ryerson University. Accessed March 04, 2021.
https://digital.library.ryerson.ca/islandora/object/RULA%3A3414.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hussein, Farah. “On the molecular release induced by ultrasound and microbubbles in cells.” 2014. Web. 04 Mar 2021.
Vancouver:
Hussein F. On the molecular release induced by ultrasound and microbubbles in cells. [Internet] [Thesis]. Ryerson University; 2014. [cited 2021 Mar 04].
Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A3414.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hussein F. On the molecular release induced by ultrasound and microbubbles in cells. [Thesis]. Ryerson University; 2014. Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A3414
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
McMaster University
2.
LLANO PIEDRA, LISSET BARBARA.
TOWARD MOLECULAR IMAGING PROBES TO DETECT CRYPTIC BACTERIAL INFECTIONS.
Degree: MSc, 2016, McMaster University
URL: http://hdl.handle.net/11375/18688
► Infectious diseases represent one of the leading causes of death globally. Prompt diagnosis is essential for the onset of clinical treatment but certain cases of…
(more)
▼ Infectious diseases represent one of the leading causes of death globally. Prompt diagnosis is essential for the onset of clinical treatment but certain cases of underlying bacterial infection deep in the body can remain undiagnosed for weeks. Hidden bacterial infection is the leading cause of fever of unknown origin (FUO), which is observed in 2 % of all hospital admissions around the world. Molecular imaging of bacterial infections is the ideal non-invasive diagnostic tool, but all available probes also detect inflammation. Two targets were selected for development of bacteria-specific molecular imaging probes, namely iron-uptake pathways and peptidoglycans involved in the synthesis of the cell wall. Both, Gram-positive and Gram-negative bacteria use iron-binding molecules called siderophores to scavenge iron from their surroundings. The structural similarities between Fe3+ and Ga3+ allow siderophores to be radiolabelled with 67/68Ga and visualized by nuclear medicine techniques. The clinically proven siderophore Deferoxamine (Dfo) has a plasma half-life of only 5.5 min that does not favor its direct use as a probe. Dfo derivatives with improved pharmacokinetics properties were designed and tested on Staphylococcus aureus cultures. The ciprofloxacin and the ethyloxycarbonyl derivatives of DFO at the primary amino position were among the most successful conjugates targeting the siderophore active-transport mechanism and reaching high relative uptake rates. Furthermore, the peptidoglycan pathway of Gram-positive bacteria was in vitro targeted with vancomycin conjugated to 67Ga-Dfo which showed even higher labelling capacity than 67Ga-Dfo within a few minutes of exposure. In vitro siderophore studies remain challenging due to the lack of methods for the preparation of rigorously iron-depleted media. We developed an iron chelating method with the goal of creating iron-free growth media.
Thesis
Master of Science (MSc)
Advisors/Committee Members: BERTI, PAUL, Chemical Biology.
Subjects/Keywords: molecular imaging of bacterial infection
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APA (6th Edition):
LLANO PIEDRA, L. B. (2016). TOWARD MOLECULAR IMAGING PROBES TO DETECT CRYPTIC BACTERIAL INFECTIONS. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/18688
Chicago Manual of Style (16th Edition):
LLANO PIEDRA, LISSET BARBARA. “TOWARD MOLECULAR IMAGING PROBES TO DETECT CRYPTIC BACTERIAL INFECTIONS.” 2016. Masters Thesis, McMaster University. Accessed March 04, 2021.
http://hdl.handle.net/11375/18688.
MLA Handbook (7th Edition):
LLANO PIEDRA, LISSET BARBARA. “TOWARD MOLECULAR IMAGING PROBES TO DETECT CRYPTIC BACTERIAL INFECTIONS.” 2016. Web. 04 Mar 2021.
Vancouver:
LLANO PIEDRA LB. TOWARD MOLECULAR IMAGING PROBES TO DETECT CRYPTIC BACTERIAL INFECTIONS. [Internet] [Masters thesis]. McMaster University; 2016. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/11375/18688.
Council of Science Editors:
LLANO PIEDRA LB. TOWARD MOLECULAR IMAGING PROBES TO DETECT CRYPTIC BACTERIAL INFECTIONS. [Masters Thesis]. McMaster University; 2016. Available from: http://hdl.handle.net/11375/18688
McMaster University
3.
Vito, Alyssa.
Preparation and Evaluation of Molecular Imaging Probes Targeting the Urokinase Plasminogen Activator System.
Degree: MSc, 2015, McMaster University
URL: http://hdl.handle.net/11375/18443
► The aim of this thesis was to develop a molecular imaging probe for the urokinase plasminogen activator (uPA) system, which has been shown to play…
(more)
▼ The aim of this thesis was to develop a molecular imaging probe for the urokinase plasminogen activator (uPA) system, which has been shown to play a critical role in cancer metastasis, tumour aggressiveness and likelihood of progression. Two classes of small molecule inhibitors carrying isotopes of iodine were synthesized and evaluated using in vitro assays and in vivo studies. Lead compounds showed high affinity for the target with Ki values in the low nanomolar range (1b = 1.4 nM, 1e = 6.1 nM, 1g = 2.6 nM and 2a = 2.1 nM). Biodistribution studies of the reversible compounds (1b, 1e, 1g) showed rapid clearance, accumulation in the gall bladder and intestines and little to no tumour uptake (<1 %ID/g). The irreversible inhibitor (2a) showed specificity for the target through SDS-PAGE and biodistribution studies. Analysis of the biodistribution pattern showed retention in the tumour over time reaching a maximum at 24 h post-injection of 1.95 %ID/g with tumour-to-blood ratio being 0.65 at 24 h, 1.13 at 48 h and 1.09 at 96 h post-injection.
A parallel strategy reported involved targeting the uPA receptor (uPAR) through the use of antibodies and bioorthogonal chemisty based on radiolabeled tetrazines and transcyclooctene (TCO) functionalized biomolecules. A new tetrazine synthon was developed that can be readily labeled with both 99mTc and 18F where the products were produced in 75 and 31 % radiochemical yields. Stability studies showed the compounds are suitable for use in vivo. Biodistribution studies were carried out in CD1 mice and results showed that both probes had sufficient distribution patterns to warrant use in pre-targeting strategies. Their reactivity with TCO, including functionalized derivatives such as TCO-anti-uPAR, was also demonstrated creating the means to develop PET and SPECT probes for imaging the urokinase system using a single prosthetic group.
Thesis
Master of Science (MSc)
Advisors/Committee Members: Valliant, John, Chemical Biology.
Subjects/Keywords: upa; cancer; molecular imaging; radiochemistry
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APA (6th Edition):
Vito, A. (2015). Preparation and Evaluation of Molecular Imaging Probes Targeting the Urokinase Plasminogen Activator System. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/18443
Chicago Manual of Style (16th Edition):
Vito, Alyssa. “Preparation and Evaluation of Molecular Imaging Probes Targeting the Urokinase Plasminogen Activator System.” 2015. Masters Thesis, McMaster University. Accessed March 04, 2021.
http://hdl.handle.net/11375/18443.
MLA Handbook (7th Edition):
Vito, Alyssa. “Preparation and Evaluation of Molecular Imaging Probes Targeting the Urokinase Plasminogen Activator System.” 2015. Web. 04 Mar 2021.
Vancouver:
Vito A. Preparation and Evaluation of Molecular Imaging Probes Targeting the Urokinase Plasminogen Activator System. [Internet] [Masters thesis]. McMaster University; 2015. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/11375/18443.
Council of Science Editors:
Vito A. Preparation and Evaluation of Molecular Imaging Probes Targeting the Urokinase Plasminogen Activator System. [Masters Thesis]. McMaster University; 2015. Available from: http://hdl.handle.net/11375/18443
Université Catholique de Louvain
4.
Neveu, Marie-Aline.
Multi-modality imaging to assess metabolic shift in tumors.
Degree: 2016, Université Catholique de Louvain
URL: http://hdl.handle.net/2078.1/179477
► The objective of the thesis was to explore the value of different noninvasive imaging technologies to assess tumor metabolic profiles in vivo and their pharmacological…
(more)
▼ The objective of the thesis was to explore the value of different noninvasive imaging technologies to assess tumor metabolic profiles in vivo and their pharmacological modulations. Adaptive behaviors supporting a deregulated metabolism in cancer represent major challenges for therapies. Therefore, a better understanding of these processes associated with the characterization of metabolic patterns in tumors would lead to the development of more efficient anticancer strategies. In parallel to in vitro characterizations, advanced imaging techniques including EPR oximetry, 13C-hyperpolarized NMR, 17O MRS and 18F-FDG PET, were used to identify the metabolic signature in well-established tumor models in vivo. Our study reveals major discordances between in vitro and in vivo metabolic profiles, highlighting the limitation of in vitro studies to truly reflect the complex tumor behavior. Using imaging modalities, we confirmed the key role of local microenvironment to shape tumor features.
(BIFA - Sciences biomédicales et pharmaceutiques) – UCL, 2016
Advisors/Committee Members: UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - Faculté de pharmacie et des sciences biomédicales, Feron, Olivier, Delzenne, Nathalie, Jordan, Bénédicte, Bindels, Laure, Grégoire, Vincent, Gallez, Bernard, Ardenkjaer-Larsen, Jan Henrik, Scheenen, Tom.
Subjects/Keywords: Molecular imaging; Tumor metabolism
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APA (6th Edition):
Neveu, M. (2016). Multi-modality imaging to assess metabolic shift in tumors. (Thesis). Université Catholique de Louvain. Retrieved from http://hdl.handle.net/2078.1/179477
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Neveu, Marie-Aline. “Multi-modality imaging to assess metabolic shift in tumors.” 2016. Thesis, Université Catholique de Louvain. Accessed March 04, 2021.
http://hdl.handle.net/2078.1/179477.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Neveu, Marie-Aline. “Multi-modality imaging to assess metabolic shift in tumors.” 2016. Web. 04 Mar 2021.
Vancouver:
Neveu M. Multi-modality imaging to assess metabolic shift in tumors. [Internet] [Thesis]. Université Catholique de Louvain; 2016. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2078.1/179477.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Neveu M. Multi-modality imaging to assess metabolic shift in tumors. [Thesis]. Université Catholique de Louvain; 2016. Available from: http://hdl.handle.net/2078.1/179477
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Johannes Gutenberg Universität Mainz
5.
Schieferstein, Hanno.
Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors.
Degree: 2013, Johannes Gutenberg Universität Mainz
URL: http://ubm.opus.hbz-nrw.de/volltexte/2013/3603/
► Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis.…
(more)
▼ Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new 18F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed 18F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable 18F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for 18F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K⊂2.2.2]+/carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved.rnThe promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were conducted. The synthesis of the folate-boron clusters was straightforward. At first, a linker molecule based on maleic acid was synthesized, which was coupled to the boron cluster via Michael Addition of a thiol and alkene and subsequently coupled to the targeting moiety using CuAAC. The new conjugates of folate and boron clusters led to a significant increase of boron concentration in the cell of about 5-times compared to currently used and approved boron pharmaceuticals. rnMoreover, azido-folate derivatives were coupled to macromolecular carrier systems (pHPMA), which showed an enhanced and specific accumulation at target sites (up to 2.5-times) during in vivo experiments. A specific blockade could be observed up to 30% indicating an efficient targeting effect. A new kind of nanoparticles consisting of a PDLLA core and p((HPMA)-b-LMA)) as surfactants were developed and successfully radiolabeled via 18F-click chemistry in good RCYs of 8±3%rnThe nanoparticles were obtained via the miniemulsion technique in combination with solvent evaporation. The 18F-labeled nanoparticles were applied to in vivo testing…
Subjects/Keywords: Molecular Imaging; Chemistry and allied sciences
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APA ·
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APA (6th Edition):
Schieferstein, H. (2013). Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors. (Doctoral Dissertation). Johannes Gutenberg Universität Mainz. Retrieved from http://ubm.opus.hbz-nrw.de/volltexte/2013/3603/
Chicago Manual of Style (16th Edition):
Schieferstein, Hanno. “Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors.” 2013. Doctoral Dissertation, Johannes Gutenberg Universität Mainz. Accessed March 04, 2021.
http://ubm.opus.hbz-nrw.de/volltexte/2013/3603/.
MLA Handbook (7th Edition):
Schieferstein, Hanno. “Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors.” 2013. Web. 04 Mar 2021.
Vancouver:
Schieferstein H. Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors. [Internet] [Doctoral dissertation]. Johannes Gutenberg Universität Mainz; 2013. [cited 2021 Mar 04].
Available from: http://ubm.opus.hbz-nrw.de/volltexte/2013/3603/.
Council of Science Editors:
Schieferstein H. Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors. [Doctoral Dissertation]. Johannes Gutenberg Universität Mainz; 2013. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2013/3603/
Penn State University
6.
Shen, Kan.
Molecular Depth Profiling and Chemical Imaging with Cluster ToF-SIMS.
Degree: 2015, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/26406
► The work presented in this dissertation is concentrated on improving the fundamental understanding of molecular depth profiling and chemical imaging associated with time-of-flight secondary ion…
(more)
▼ The work presented in this dissertation is concentrated on improving the fundamental understanding of
molecular depth profiling and chemical
imaging associated with time-of-flight secondary ion mass spectrometry (ToF-SIMS) equipped with cluster ion sources, mainly C60 and argon gas cluster ion beams (Ar-GCIBs). A gold-cholesterol hybrid system is used to elucidate the reasons for the difficulties of depth profiling of heterogeneous thin film structures. The model study provides mechanistic insight into depth profiling of hybrid materials and offers an appropriate strategy for improving the quality of the depth profiles. Depth profiling of trehalose thin films is investigated under different Ar-GCIBs bombardment conditions to elucidate the influence of cluster size and kinetic energy on the formation of
molecular ions. The study provides insight into selecting optimal Ar-GCIBs characteristics for
molecular depth profiling of organic materials. Finally, room temperature ionic liquids (ILs) are employed in mass spectrometry
imaging experiments. The surface and the internal structure of microspheres synthesized in ILs are investigated by the high spatial resolution
imaging and depth profiling capabilities of cluster ToF-SIMS. The study introduces a new type of matrix for
imaging mass spectrometry and provides insight into the key drivers and restraints behind ToF-SIMS three-dimensional (3D)
molecular analysis. Overall, the thesis work is of great value for the fundamental understanding cluster ion-solid interactions in ToF-SIMS analysis and is beneficial for the advancement of the technique.
Advisors/Committee Members: Nicholas Winograd, Dissertation Advisor/Co-Advisor, Nicholas Winograd, Committee Chair/Co-Chair, Barbara Jane Garrison, Committee Member, Christine Dolan Keating, Committee Member, Yingwei Mao, Committee Member.
Subjects/Keywords: ToF-SIMS; molecular depth profiling; chemical imaging
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APA (6th Edition):
Shen, K. (2015). Molecular Depth Profiling and Chemical Imaging with Cluster ToF-SIMS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/26406
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Shen, Kan. “Molecular Depth Profiling and Chemical Imaging with Cluster ToF-SIMS.” 2015. Thesis, Penn State University. Accessed March 04, 2021.
https://submit-etda.libraries.psu.edu/catalog/26406.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shen, Kan. “Molecular Depth Profiling and Chemical Imaging with Cluster ToF-SIMS.” 2015. Web. 04 Mar 2021.
Vancouver:
Shen K. Molecular Depth Profiling and Chemical Imaging with Cluster ToF-SIMS. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Mar 04].
Available from: https://submit-etda.libraries.psu.edu/catalog/26406.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shen K. Molecular Depth Profiling and Chemical Imaging with Cluster ToF-SIMS. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/26406
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
7.
Lin, Mai.
Molecular Imaging of αvβ6–Positive Tumors and Pancreatic β-Cell Mass by Radiolabeled Peptides.
Degree: 2011, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/856
► Conventional diagnostic methodologies of lung cancer and diabetes are limited by sensitivity and specificity. In consequence, patients usually get diagnosed when the symptoms appear and…
(more)
▼ Conventional diagnostic methodologies of lung cancer and diabetes are limited by sensitivity and specificity. In consequence, patients usually get diagnosed when the symptoms appear and the diseases are at the advanced stages. As the expressions of the avß6 integrin and glucagon-like peptide-1 receptor (GLP-1R) are highly related to aggressive tumor phenotypes and functional pancreatic ß-cells, this work has been set to develop peptide-based radiotracers that can specifically bind to avß6 or GLP-1R for noninvasively monitoring the progression of lung cancer and diabetes.
By phage display, a peptide sequence that specific binds to avß6 was identified. In the evaluation of its truncated forms with similar binding affinity, a polyethylene glycol chain (PEG11) was inserted to the C-terminus and a bifunctional chelator (DOTA) was conjugated to either end of the peptides. The conjugates were labeled with 111In (t1/2: 2.8 d) under mild conditions with the highest achievable specific activity of 1.15 × 104 MBq/µmol. The in vivo evaluation was performed in a lung adenocarcinoma xenograft mouse model. Of the six conjugates, 10PD showed the best tissue contrast of the H2009 (avß6+) tumor. However, it also yielded to have the highest renal accumulation. The high kidney uptake of 10PD was found to be alleviated by conjugating DOTA at the N-terminus or reducing the peptide net charges.
To evaluate GLP-1-based radiotracers for
imaging pancreatic ß-cell mass (BCM), GLP-1, [D-Ala8]GLP-1, two bicyclic GLP-1 analogs (EM2196 and EM2198), and exendin-4 were synthesized and compared for their biological properties. All peptide constructs were tagged with an 6-aminohexanoic linker (Ahx) followed by DOTA conjugation at C-terminus and labeled with 64Cu (t1/2: 12.7 h). The specific activity of the labeled peptide conjugates was up to 1.0 × 106 MBq/µmol with radiochemical purity over 97%. Compared to GLP-1, [D-Ala8]GLP-1 revealed strong resistance against DPP-IV. In addition, EM2198 demonstrated high stability against NEP 24.11 presumably by the shielding effects from the two lactam bridges. All peptide conjugates were highly selective to the GLP-1R with the IC50 values in 0.1-0.4 nM. However, only 64Cu-EM2198 showed clear pancreas area on the microPET/CT studies. The signal of 64Cu-EM2198 from the pancreas was confirmed by the ex vivo
imaging scans. The potential of 64Cu-EM2198 for
imaging BCM was further supported by co-injecting a blocking dose of unlabeled exendin-4 and performing
imaging studies in the STZ-treated diabetic mice.
Advisors/Committee Members: Sun, Xiankai.
Subjects/Keywords: Diabetes Mellitus; Lung Neoplasms; Integrins; Molecular Imaging
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APA ·
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APA (6th Edition):
Lin, M. (2011). Molecular Imaging of αvβ6–Positive Tumors and Pancreatic β-Cell Mass by Radiolabeled Peptides. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/856
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lin, Mai. “Molecular Imaging of αvβ6–Positive Tumors and Pancreatic β-Cell Mass by Radiolabeled Peptides.” 2011. Thesis, University of Texas Southwestern Medical Center. Accessed March 04, 2021.
http://hdl.handle.net/2152.5/856.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lin, Mai. “Molecular Imaging of αvβ6–Positive Tumors and Pancreatic β-Cell Mass by Radiolabeled Peptides.” 2011. Web. 04 Mar 2021.
Vancouver:
Lin M. Molecular Imaging of αvβ6–Positive Tumors and Pancreatic β-Cell Mass by Radiolabeled Peptides. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2152.5/856.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lin M. Molecular Imaging of αvβ6–Positive Tumors and Pancreatic β-Cell Mass by Radiolabeled Peptides. [Thesis]. University of Texas Southwestern Medical Center; 2011. Available from: http://hdl.handle.net/2152.5/856
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Columbia University
8.
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 (6th 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 (16th Edition):
Fiala, Tomas. “Polymer supported probes and drugs for targeted brain imaging and pharmacology.” 2020. Doctoral Dissertation, Columbia University. Accessed March 04, 2021.
https://doi.org/10.7916/d8-dbv1-gp60.
MLA Handbook (7th Edition):
Fiala, Tomas. “Polymer supported probes and drugs for targeted brain imaging and pharmacology.” 2020. Web. 04 Mar 2021.
Vancouver:
Fiala T. Polymer supported probes and drugs for targeted brain imaging and pharmacology. [Internet] [Doctoral dissertation]. Columbia University; 2020. [cited 2021 Mar 04].
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 Ottawa
9.
Tayyabi, Ehsen.
Gone Fishing: Synthesis and Design of a Superparamagnetic Nanobait for Trapping Reactive Metabolites In Vivo.
Degree: 2018, University of Ottawa
URL: http://hdl.handle.net/10393/37338
► Adverse drug reactions are common causes of medical injuries. Drug-induced hepatotoxicity remains one of the leading causes of emergency room visits, FDA non-approval, and drug…
(more)
▼ Adverse drug reactions are common causes of medical injuries. Drug-induced hepatotoxicity remains one of the leading causes of emergency room visits, FDA non-approval, and drug withdrawal from the market. We have investigated the ability of endogenous nucleophilic amino acid residues (K, H, and C) to selectively bind to reactive electrophilic drug metabolites, focusing on acetyl-para-aminophenol (APAP, i.e. Tylenol®), for which hepatotoxicity has recently re- emerged as a major health concern for Canadians. Three peptide sequences were synthesized bearing terminal nucleophilic residues, brominated phenylalanine residues, and c-terminal amides. These peptides were coupled to carboxy methyl dextran coated iron oxide nanoparticles (CMX- IONPs) with a hepatocyte targeting group. IONPs are known for their ability to act as T2-weighted MRI contrast agents, giving us the ability to track them in vivo. This study begins to establish a nanotechnology-based method for the in vivo trapping of NAPQI, the reactive metabolite of APAP, using a cysteine bearing IONP.
Subjects/Keywords: Molecular Imaging;
Chemical Biology;
MRI;
Drug Metabolism
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Chicago ·
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APA (6th Edition):
Tayyabi, E. (2018). Gone Fishing: Synthesis and Design of a Superparamagnetic Nanobait for Trapping Reactive Metabolites In Vivo.
(Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/37338
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Tayyabi, Ehsen. “Gone Fishing: Synthesis and Design of a Superparamagnetic Nanobait for Trapping Reactive Metabolites In Vivo.
” 2018. Thesis, University of Ottawa. Accessed March 04, 2021.
http://hdl.handle.net/10393/37338.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tayyabi, Ehsen. “Gone Fishing: Synthesis and Design of a Superparamagnetic Nanobait for Trapping Reactive Metabolites In Vivo.
” 2018. Web. 04 Mar 2021.
Vancouver:
Tayyabi E. Gone Fishing: Synthesis and Design of a Superparamagnetic Nanobait for Trapping Reactive Metabolites In Vivo.
[Internet] [Thesis]. University of Ottawa; 2018. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10393/37338.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tayyabi E. Gone Fishing: Synthesis and Design of a Superparamagnetic Nanobait for Trapping Reactive Metabolites In Vivo.
[Thesis]. University of Ottawa; 2018. Available from: http://hdl.handle.net/10393/37338
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Uppsala University
10.
Lövgren, Jessica.
Site-specific labelling of anti-HER2 ADAPT proteins for molecular imaging applications.
Degree: Biology Education Centre, 2016, Uppsala University
URL: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-302905
► Cancer is one of the leading causes of death worldwide. It is of great importance to use reliable diagnostic methods before determining treatment methods.…
(more)
▼ Cancer is one of the leading causes of death worldwide. It is of great importance to use reliable diagnostic methods before determining treatment methods. Molecular imaging is a non-invasive approach of visualising tumours in vivo. This method requires imaging agents that are detectable and binds specifically to the tumour. The aim of this degree project was to produce and characterise a protein-based imaging agent, called ADAPT, that has been engineered to bind the breast cancer associated receptor HER2. This protein has previously been labelled with radionuclides in the N-terminal and tested in vivo with promising results. However, due to the fact that the position of the radiolabel can affect the biodistribution of the imaging agent, a comparison to C-terminal radiolabelled variants is of high interest. Radiolabelling can be performed by first attaching a chelator to the protein and later bind the radionuclide through the chelator. The chelator used in this project binds to a thiol group and therefore a unique cysteine was added to the C-termini. The N-termini were altered to both generate variants with and without purification tag. Proteins with altered N-termini and C-termini were produced and later characterised by circular dichroism and surface plasmon resonance. None of the non-tagged variants could be produced to a sufficient amount and was discarded for further studies. However, all variants with a purification tag could be produced and the shortest variant was chosen to be tested in vivo.
Subjects/Keywords: cancer diagnostics; molecular imaging; ADAPT; HER2
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APA (6th Edition):
Lövgren, J. (2016). Site-specific labelling of anti-HER2 ADAPT proteins for molecular imaging applications. (Thesis). Uppsala University. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-302905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lövgren, Jessica. “Site-specific labelling of anti-HER2 ADAPT proteins for molecular imaging applications.” 2016. Thesis, Uppsala University. Accessed March 04, 2021.
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-302905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lövgren, Jessica. “Site-specific labelling of anti-HER2 ADAPT proteins for molecular imaging applications.” 2016. Web. 04 Mar 2021.
Vancouver:
Lövgren J. Site-specific labelling of anti-HER2 ADAPT proteins for molecular imaging applications. [Internet] [Thesis]. Uppsala University; 2016. [cited 2021 Mar 04].
Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-302905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lövgren J. Site-specific labelling of anti-HER2 ADAPT proteins for molecular imaging applications. [Thesis]. Uppsala University; 2016. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-302905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
11.
Al-saden, Noor Mohammed Hussein.
Development of PET Imaging Probes for Predicting Response of Breast Cancer to Trastuzumab Emtansine (T-DM1).
Degree: PhD, 2019, University of Toronto
URL: http://hdl.handle.net/1807/97037
► The human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-20% of breast cancers (BC) and represents an aggressive tumour phenotype conferring a poor…
(more)
▼ The human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-20% of breast cancers (BC) and represents an aggressive tumour phenotype conferring a poor prognosis in patients. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for treatment of advanced and metastatic HER2-positive BC. Despite the efficacy of T-DM1 and lower side effects compared to conventional chemotherapy, many eligible patients do not respond. The thesis hypothesis is PET
imaging that probes T-DM1 delivery to tumours and its ability to mediate HER2 downregulation would be useful in predicting the response to T-DM1 treatment. An in vivo comparison revealed that 89Zr-DFO-T-DM1 exhibited significantly higher uptake than 89Zr-DFO-trastuzumab in mice with HER2-positive BC xenografts suggesting that 89Zr-DFO-T-DM1 may be more effective to study the delivery of T-DM1 to tumours. The correlation between tumour HER2 density, uptake of 89Zr-DFO-T-DM1, response to T-DM1, and in vitro cytotoxicity to T-DM1 was studied. There was a non-linear but direct correlation between the tumour to blood (T/B) ratios for 89Zr-DFO-T-DM1 and HER2 expression (r2=1.00). There was a direct linear correlation between the T/B ratio for 89Zr-DFO-T-DM1 and tumour doubling ratio (r2=0.97). In addition, in vitro cytotoxicity of T-DM1 demonstrated an inverse correlation with tumour doubling ratio and T/B ratio in mice treated with T-DM1 (r2=1.00). The ability of microPET/CT using 64Cu-NOTA-pertuzumab Fab fragments to detect decreased HER2 expression on tumours in vivo in NOD/SCID mice after T-DM1 treatment was also studied. However, instead of reduced tumour uptake of the
imaging probe after T-DM1 treatment, an increase was observed. Further ex vivo analysis of the tumour vasculature showed reduced blood vessel density suggesting that T-DM1 caused normalization of vessels in the tumour microenvironment which increased the uptake of the
imaging probe. I conclude that PET is a promising tool for
imaging response of HER2-positive BC to treatment with T-DM1.
Advisors/Committee Members: Reilly, Raymond, Pharmaceutical Sciences.
Subjects/Keywords: Breast Cancer; Molecular imaging; Trastuzumab Emtansine; 0572
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to Zotero / EndNote / Reference
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APA (6th Edition):
Al-saden, N. M. H. (2019). Development of PET Imaging Probes for Predicting Response of Breast Cancer to Trastuzumab Emtansine (T-DM1). (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/97037
Chicago Manual of Style (16th Edition):
Al-saden, Noor Mohammed Hussein. “Development of PET Imaging Probes for Predicting Response of Breast Cancer to Trastuzumab Emtansine (T-DM1).” 2019. Doctoral Dissertation, University of Toronto. Accessed March 04, 2021.
http://hdl.handle.net/1807/97037.
MLA Handbook (7th Edition):
Al-saden, Noor Mohammed Hussein. “Development of PET Imaging Probes for Predicting Response of Breast Cancer to Trastuzumab Emtansine (T-DM1).” 2019. Web. 04 Mar 2021.
Vancouver:
Al-saden NMH. Development of PET Imaging Probes for Predicting Response of Breast Cancer to Trastuzumab Emtansine (T-DM1). [Internet] [Doctoral dissertation]. University of Toronto; 2019. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1807/97037.
Council of Science Editors:
Al-saden NMH. Development of PET Imaging Probes for Predicting Response of Breast Cancer to Trastuzumab Emtansine (T-DM1). [Doctoral Dissertation]. University of Toronto; 2019. Available from: http://hdl.handle.net/1807/97037
University of Melbourne
12.
Yap, May Lin.
Activated platelets and antibody opsonization as tumor markers: novel avenues for cancer diagnosis, targeted therapy and monitoring therapeutic outcomes.
Degree: 2018, University of Melbourne
URL: http://hdl.handle.net/11343/221170
► With over 100 types of cancer known, the study presented in this thesis introduces novel means of targeting a wide range of cancers, rather than…
(more)
▼ With over 100 types of cancer known, the study presented in this thesis introduces novel means of targeting a wide range of cancers, rather than a specific cancer antigen. Here, unique cancer targets, such as components of the tumor microenvironment and monoclonal antibody opsonization are investigated as new approaches for cancer diagnosis and targeted therapy. The first part of the study investigates the possibility of targeting activated platelets in the tumor microenvironment as a novel cancer diagnostic target. I showed the feasibility of using a single-chain antibody, which targets the activated form of GPIIb/IIIa, the most abundant platelet-specific receptor on the platelet surface as a possible tool for cancer diagnosis using PET/CT, fluorescence imaging and ultrasound. The second part of the investigation aims to further expand the utility of the single-chain antibody as an antibody-drug conjugate for cancer therapy. Using a mouse metastasis model of triple negative breast cancer, I showed that the activated platelet targeting single-chain antibody, conjugated to Auristatin E, a clinically available chemotherapy agent, was successful in reducing tumor growth and preventing metastasis development. The final part of the thesis describes the development of an FcγRIIIa receptor dimer, which has been engineered to selectively bind avidly to multimeric Fc complexes. This binding mimics the engagement of FcγRIIIa on effector cells, such as on NK cells, with antibody-coated cells that leads to antibody-mediated target killing. Here, using a mouse xenograft model of B cell lymphoma treated with Rituximab and triple negative breast cancer adenocarcinoma, treated with an EGFR receptor antibody, I show that the FcγRIIIa receptor dimer, labeled with a near-infrared contrast agent, could be used to specifically image antibody opsonization of tumor cells in vivo.
Subjects/Keywords: molecular imaging; activated platelets; cancer; Fc receptor
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APA ·
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MLA ·
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Export
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APA (6th Edition):
Yap, M. L. (2018). Activated platelets and antibody opsonization as tumor markers: novel avenues for cancer diagnosis, targeted therapy and monitoring therapeutic outcomes. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/221170
Chicago Manual of Style (16th Edition):
Yap, May Lin. “Activated platelets and antibody opsonization as tumor markers: novel avenues for cancer diagnosis, targeted therapy and monitoring therapeutic outcomes.” 2018. Doctoral Dissertation, University of Melbourne. Accessed March 04, 2021.
http://hdl.handle.net/11343/221170.
MLA Handbook (7th Edition):
Yap, May Lin. “Activated platelets and antibody opsonization as tumor markers: novel avenues for cancer diagnosis, targeted therapy and monitoring therapeutic outcomes.” 2018. Web. 04 Mar 2021.
Vancouver:
Yap ML. Activated platelets and antibody opsonization as tumor markers: novel avenues for cancer diagnosis, targeted therapy and monitoring therapeutic outcomes. [Internet] [Doctoral dissertation]. University of Melbourne; 2018. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/11343/221170.
Council of Science Editors:
Yap ML. Activated platelets and antibody opsonization as tumor markers: novel avenues for cancer diagnosis, targeted therapy and monitoring therapeutic outcomes. [Doctoral Dissertation]. University of Melbourne; 2018. Available from: http://hdl.handle.net/11343/221170
University of Arizona
13.
Sinharay, Sanhita.
Development and Application of CatalyCEST MRI Contrast Agents for the Study of Enzyme Activities in Tumor Models
.
Degree: 2016, University of Arizona
URL: http://hdl.handle.net/10150/612945
► The in vivo detection of enzyme activity is a significant biomarker in tumorigenesis. Assessment of enzyme activity relative to enzyme concentration can serve as quite…
(more)
▼ The in vivo detection of enzyme activity is a significant biomarker in tumorigenesis. Assessment of enzyme activity relative to enzyme concentration can serve as quite an accurate measurement of several disease states. Chemical Exchange Saturation Transfer (CEST) MRI is a non-invasive
imaging technique that can be used to evaluate enzyme activity. Compared to other contrast agents CEST MRI agents have a slower chemical exchange rate and thus have greater specificity for detecting the intended biomarker. Chapter 1 provides an overview of the advances made in the field of
molecular imaging for detection of cancer biomarkers. The
molecular mechanism of each technique is explained with specific examples and advantages as well as disadvantages of each technique. Chapter 2 investigates the specific example of detection of an enzyme, γ-glutamyl transferase (GGT) in ovarian cancer tumor models using a catalyCEST MRI contrast agent. This chapter discusses the step-by step evaluation of the non-metallic contrast agent, from synthesis to evaluation of its catalytic efficiency with Michaelis Menten kinetics studies and finally in vivo GGT detection in ovarian tumor models of OVCAR-8 and OVCAR-3. Chapter 3 investigates the enzyme, Kallikrein-6 and its detection in HCT116 colon cancer tumor model. In addition to enzyme detection, enzyme inhibition using Antithrombin III inhibitor has also been explored within in vitro media and in vivo HCT116 tumor model. Chapter 4 introduces the catalyCEST agent for detection of sulfatase enzyme. This chapter discusses the synthesis of this agent and its ability to detect sulfatase in bacterial cell suspension and mammalian cell suspension. These examples portray catalyCEST MRI as a platform technology for enzyme activity detection. Finally in Chapter 5 future ideas have been proposed to improve the in vivo detection and broaden the applications of catalyCEST MRI in the field of enzyme studies.
Advisors/Committee Members: Pagel, Mark D (advisor), Kuo, Philip H. (committeemember), Glass, Richard S. (committeemember), Mash, Eugene A. (committeemember), Pagel, Mark D. (committeemember).
Subjects/Keywords: Enzymes;
Molecular Imaging;
Chemistry;
CEST MRI
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APA (6th Edition):
Sinharay, S. (2016). Development and Application of CatalyCEST MRI Contrast Agents for the Study of Enzyme Activities in Tumor Models
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/612945
Chicago Manual of Style (16th Edition):
Sinharay, Sanhita. “Development and Application of CatalyCEST MRI Contrast Agents for the Study of Enzyme Activities in Tumor Models
.” 2016. Doctoral Dissertation, University of Arizona. Accessed March 04, 2021.
http://hdl.handle.net/10150/612945.
MLA Handbook (7th Edition):
Sinharay, Sanhita. “Development and Application of CatalyCEST MRI Contrast Agents for the Study of Enzyme Activities in Tumor Models
.” 2016. Web. 04 Mar 2021.
Vancouver:
Sinharay S. Development and Application of CatalyCEST MRI Contrast Agents for the Study of Enzyme Activities in Tumor Models
. [Internet] [Doctoral dissertation]. University of Arizona; 2016. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10150/612945.
Council of Science Editors:
Sinharay S. Development and Application of CatalyCEST MRI Contrast Agents for the Study of Enzyme Activities in Tumor Models
. [Doctoral Dissertation]. University of Arizona; 2016. Available from: http://hdl.handle.net/10150/612945
University of Edinburgh
14.
Joshi, Nikhil Vilas.
Novel molecular imaging of cardiovascular disease in man.
Degree: PhD, 2016, University of Edinburgh
URL: http://hdl.handle.net/1842/25394
► Cardiovascular disease remains the commonest cause of death worldwide. The majority of deaths are caused by atherosclerotic plaque rupture with resultant myocardial infarction or stroke,…
(more)
▼ Cardiovascular disease remains the commonest cause of death worldwide. The majority of deaths are caused by atherosclerotic plaque rupture with resultant myocardial infarction or stroke, or rupture of abdominal aortic aneurysms. Conventional imaging modalities have consistently failed to identify atherosclerotic plaques or aneurysms with high-risk pathological features that are at highest risk of rupture or progression. The development of modern molecular imaging techniques targeted at these features could lead to the identification of such high-risk plaques and aneurysms in vivo and guide the development of novel treatment strategies. The aim of this thesis was to evaluate whether novel molecular modalities have a role in providing new insights into biological disease processes, and identify high-risk plaques and aneurysms. Using positron emission tomography-computed tomography (PET-CT), 18F-fluorodeoxyglucose and 18F-fluoride were utilised as markers of metabolic inflammation and active calcification. Cellular inflammation was assessed using ultrasmall superparamagnetic particles of iron oxide (USPIO) enhanced magnetic resonance imaging (MRI). In a prospective trial, 80 patients with myocardial infarction (n=40) and stable angina (n=40) underwent 18F-fluoride and 18F-fluorodeoxyglucose PET-CT, and invasive coronary angiography (Chapter 3). Intense 18F-fluoride uptake localised to recently ruptured plaque in patients with acute myocardial infarction. In patients with stable coronary artery disease, 18F-fluoride uptake identified coronary plaques with high-risk features on intravascular ultrasound. 18F-fluoride PET-CT is the first noninvasive imaging method to identify and localise ruptured and high-risk coronary plaques. Aortic vascular uptake of 18F- fluorodeoxyglucose was studied in patients with myocardial infarction and stable angina (Chapter 4). In a separate outcome of 1,003 patients enrolled in the Global Registry of Acute Coronary Events, we further evaluated whether infarct size predicted recurrent coronary events. Patients with myocardial infarction had higher remote atherosclerotic tracer uptake that correlated with the degree of myocardial necrosis, and exceeded that observed in patients with stable coronary disease. The outcome cohort demonstrated that patients with higher degree of myocardial necrosis had the highest risk of early recurrent myocardial infarction. This supports the hypothesis that acute myocardial infarction exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: myocardial infarction begets myocardial infarction. In a prospective imaging cohort, the role inflammation and calcification was assessed in 63 patients with abdominal aortic aneurysms and 19 age and sex matched patients with atherosclerosis (Chapter 5). Compared to non-aneurysmal segments, enhanced inflammation and calcification was observed within the wall of aortic aneurysmal segments. In comparison to matched controls with atherosclerosis, the entire aorta in those with aortic aneurysm appears…
Subjects/Keywords: 616.1; atherosclerosis; aneurysm; molecular imaging; PET-CT
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Joshi, N. V. (2016). Novel molecular imaging of cardiovascular disease in man. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/25394
Chicago Manual of Style (16th Edition):
Joshi, Nikhil Vilas. “Novel molecular imaging of cardiovascular disease in man.” 2016. Doctoral Dissertation, University of Edinburgh. Accessed March 04, 2021.
http://hdl.handle.net/1842/25394.
MLA Handbook (7th Edition):
Joshi, Nikhil Vilas. “Novel molecular imaging of cardiovascular disease in man.” 2016. Web. 04 Mar 2021.
Vancouver:
Joshi NV. Novel molecular imaging of cardiovascular disease in man. [Internet] [Doctoral dissertation]. University of Edinburgh; 2016. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1842/25394.
Council of Science Editors:
Joshi NV. Novel molecular imaging of cardiovascular disease in man. [Doctoral Dissertation]. University of Edinburgh; 2016. Available from: http://hdl.handle.net/1842/25394
University of Manchester
15.
Carrascal Minino, Amaia.
The use of spin traps and spin scavengers for imaging
oxidative damage.
Degree: 2019, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319465
► Spin traps and scavengers have been used to detect free radicals for decades. They react with free radical molecules forming adducts that either prolong the…
(more)
▼ Spin traps and scavengers have been used to detect
free radicals for decades. They react with free radical molecules
forming adducts that either prolong the free radical signal (spin
traps) or void it (spin scavengers). This reactivity has been
exploited in electron spin resonance (ESR), a technique that
despite its low sensitivity it is still considered the gold
standard to detect free radicals. In this thesis the aim was to
test if spin traps and spin scavengers could be adapted to other
analytical modalities with more sensitivity and/or quantification
capabilities. The infrastructures available allowed us to consider
positron emission tomography (PET) and mass spectrometry (LC-MS and
imaging). Firstly the molecules were evaluated in in vitro
competition experiments using LC-MS. A simple method to evaluate
oxidative damage products was developed, and commercially available
spin traps and scavengers were tested. The experimental results
agreed with the literature pointing towards DMPO
(5,5-dimethyl-1-pyrroline- N oxide) like molecules as suitable
tracers. In the second results chapters three F-18 PET tracers with
spin trap or scavenger reactivity were produced and tested in cell
uptake experiments. The experiments were negative for uptake. The
third part of the thesis was planned for investigation of the
mechanism of action of the successful PET tracer but also to
develop a technique that would allow the identification of radical
damaged biomolecules with mass spectrometry
imaging. Only a very
low intensity peak could be assigned to a possible radical
oxidation. The main conclusion of these experiments is that the
mass spectrometry
imaging (MSI) used might not have enough
sensitivity and mass resolution to study these low intensity peaks.
The hypothesis that spin traps and spin scavengers could be
exploited with other techniques was explored in this thesis in
different ways without promising results.
Advisors/Committee Members: PRENANT, CHRISTIAN C, WILLIAMS, KAYE KJ, Mcmahon, Adam, Prenant, Christian, Williams, Kaye.
Subjects/Keywords: oxidative damage; radiotherapy; PET; MSI; molecular imaging
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APA ·
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MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Carrascal Minino, A. (2019). The use of spin traps and spin scavengers for imaging
oxidative damage. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319465
Chicago Manual of Style (16th Edition):
Carrascal Minino, Amaia. “The use of spin traps and spin scavengers for imaging
oxidative damage.” 2019. Doctoral Dissertation, University of Manchester. Accessed March 04, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319465.
MLA Handbook (7th Edition):
Carrascal Minino, Amaia. “The use of spin traps and spin scavengers for imaging
oxidative damage.” 2019. Web. 04 Mar 2021.
Vancouver:
Carrascal Minino A. The use of spin traps and spin scavengers for imaging
oxidative damage. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2021 Mar 04].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319465.
Council of Science Editors:
Carrascal Minino A. The use of spin traps and spin scavengers for imaging
oxidative damage. [Doctoral Dissertation]. University of Manchester; 2019. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319465
University of Cambridge
16.
Chowdhury, Mohammed.
Multi-modality Imaging to Determine the Role of Calcification and Inflammation on Restenosis Rates Following Lower Limb Angioplasty.
Degree: PhD, 2020, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/306869
► Peripheral arterial disease (PAD) is a major cause of CVD-related death and disability. Restenosis is common, occurring in 40-60% of cases at 12 months following…
(more)
▼ Peripheral arterial disease (PAD) is a major cause of CVD-related death and disability. Restenosis is common, occurring in 40-60% of cases at 12 months following lower extremity percutaneous transluminal angioplasty (PTA). No such method exists to identify patients who are at risk from restenosis before intervention. Tracers of inflammation (18F-FDG; fluorodeoxyglucose) and calcification (18F-NaF; sodium fluoride) are higher in restenosis following lower limb angioplasty in patients with peripheral arterial disease, and drug-coated balloons (DCB) dampen the inflammatory process, in an atherosclerotic rabbit model. In the prospective clinical study arm (CA), 50 patients with symptomatic PAD underwent 18F-NaF and 18F-FDG PET imaging of the superficial femoral artery (SFA), pre- and 6-weeks post-angioplasty. The primary outcome was restenosis at 12 months. DCB PTA was studied (compared to plain PTA) using near infrared fluorescence-optical coherence tomography hybrid imaging (NIRF-OCT) and plaque burden assessed by intravascular ultrasound (IVUS), in the experimental arm (EA). 40 patients were used for formal analysis. 14 patients (35%) reached the primary outcome of restenosis. Pre-PTA TBRmax in the restenosis group for 18F-FDG (2.43 [IQR 2.29 – 2.61] and 18F-NaF (2.61 [IQR 2.50 – 2.77]) were higher than the no-restenosis equivalent groups (1.63 [IQR 1.52 – 1.78] and 1.69 [IQR 1.54 – 1.77], p< 0.001). Furthermore, in the no-restenosis group there was a drop in both 18F-FDG and 18F-NaF tracer uptake (p=0.034 and 0.047, respectively) between the two timepoints; a finding not observed in the restenosis group. Experimentally, Plaque pathobiology assessment using NIRF after PTA vs. DCB treatment (42.91 nM vs 17.35 nM, p = 0.028) favoured DCB use to reduce inflammatory effects of angioplasty. Furthermore, DCB use demonstrated neointimal area regression (-2.55 % [IQR -5.35 to -0.43]) versus growth with PTA use (+6.29% [IQR 4.20 – 7.79]; p =0.002), as assessed by IVUS. Together our findings suggest that non-invasive and invasive structural-molecular imaging provide unique but complementary insights into the pathophysiology of restenosis, specifically inflammatory and calcific mediators of arterial remodelling following injury.
Subjects/Keywords: PAD; Molecular imaging; PET/CT; Restenosis
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APA (6th Edition):
Chowdhury, M. (2020). Multi-modality Imaging to Determine the Role of Calcification and Inflammation on Restenosis Rates Following Lower Limb Angioplasty. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/306869
Chicago Manual of Style (16th Edition):
Chowdhury, Mohammed. “Multi-modality Imaging to Determine the Role of Calcification and Inflammation on Restenosis Rates Following Lower Limb Angioplasty.” 2020. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021.
https://www.repository.cam.ac.uk/handle/1810/306869.
MLA Handbook (7th Edition):
Chowdhury, Mohammed. “Multi-modality Imaging to Determine the Role of Calcification and Inflammation on Restenosis Rates Following Lower Limb Angioplasty.” 2020. Web. 04 Mar 2021.
Vancouver:
Chowdhury M. Multi-modality Imaging to Determine the Role of Calcification and Inflammation on Restenosis Rates Following Lower Limb Angioplasty. [Internet] [Doctoral dissertation]. University of Cambridge; 2020. [cited 2021 Mar 04].
Available from: https://www.repository.cam.ac.uk/handle/1810/306869.
Council of Science Editors:
Chowdhury M. Multi-modality Imaging to Determine the Role of Calcification and Inflammation on Restenosis Rates Following Lower Limb Angioplasty. [Doctoral Dissertation]. University of Cambridge; 2020. Available from: https://www.repository.cam.ac.uk/handle/1810/306869
University of Manchester
17.
Carrascal Minino, Amaia.
The use of spin traps and spin scavengers for imaging oxidative damage.
Degree: PhD, 2019, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/the-use-of-spin-traps-and-spin-scavengers-for-imaging-oxidative-damage(6c9f5f57-2631-4b10-bc21-7cd0544b8f1d).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823182
► Spin traps and scavengers have been used to detect free radicals for decades. They react with free radical molecules forming adducts that either prolong the…
(more)
▼ Spin traps and scavengers have been used to detect free radicals for decades. They react with free radical molecules forming adducts that either prolong the free radical signal (spin traps) or void it (spin scavengers). This reactivity has been exploited in electron spin resonance (ESR), a technique that despite its low sensitivity it is still considered the gold standard to detect free radicals. In this thesis the aim was to test if spin traps and spin scavengers could be adapted to other analytical modalities with more sensitivity and/or quantification capabilities. The infrastructures available allowed us to consider positron emission tomography (PET) and mass spectrometry (LC-MS and imaging). Firstly the molecules were evaluated in in vitro competition experiments using LC-MS. A simple method to evaluate oxidative damage products was developed, and commercially available spin traps and scavengers were tested. The experimental results agreed with the literature pointing towards DMPO (5,5-dimethyl-1-pyrroline- N oxide) like molecules as suitable tracers. In the second results chapters three F-18 PET tracers with spin trap or scavenger reactivity were produced and tested in cell uptake experiments. The experiments were negative for uptake. The third part of the thesis was planned for investigation of the mechanism of action of the successful PET tracer but also to develop a technique that would allow the identification of radical damaged biomolecules with mass spectrometry imaging. Only a very low intensity peak could be assigned to a possible radical oxidation. The main conclusion of these experiments is that the mass spectrometry imaging (MSI) used might not have enough sensitivity and mass resolution to study these low intensity peaks. The hypothesis that spin traps and spin scavengers could be exploited with other techniques was explored in this thesis in different ways without promising results.
Subjects/Keywords: oxidative damage; radiotherapy; PET; MSI; molecular imaging
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APA (6th Edition):
Carrascal Minino, A. (2019). The use of spin traps and spin scavengers for imaging oxidative damage. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/the-use-of-spin-traps-and-spin-scavengers-for-imaging-oxidative-damage(6c9f5f57-2631-4b10-bc21-7cd0544b8f1d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823182
Chicago Manual of Style (16th Edition):
Carrascal Minino, Amaia. “The use of spin traps and spin scavengers for imaging oxidative damage.” 2019. Doctoral Dissertation, University of Manchester. Accessed March 04, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/the-use-of-spin-traps-and-spin-scavengers-for-imaging-oxidative-damage(6c9f5f57-2631-4b10-bc21-7cd0544b8f1d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823182.
MLA Handbook (7th Edition):
Carrascal Minino, Amaia. “The use of spin traps and spin scavengers for imaging oxidative damage.” 2019. Web. 04 Mar 2021.
Vancouver:
Carrascal Minino A. The use of spin traps and spin scavengers for imaging oxidative damage. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2021 Mar 04].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-use-of-spin-traps-and-spin-scavengers-for-imaging-oxidative-damage(6c9f5f57-2631-4b10-bc21-7cd0544b8f1d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823182.
Council of Science Editors:
Carrascal Minino A. The use of spin traps and spin scavengers for imaging oxidative damage. [Doctoral Dissertation]. University of Manchester; 2019. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-use-of-spin-traps-and-spin-scavengers-for-imaging-oxidative-damage(6c9f5f57-2631-4b10-bc21-7cd0544b8f1d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823182
University of Georgia
18.
Langley, Jason Allen.
Estimation of the phase gradient in MIR.
Degree: 2014, University of Georgia
URL: http://hdl.handle.net/10724/27201
► Images acquired from magnetic resonance imaging scanners take complex values. The images can be broken into two distinct types of images: magnitude images and phase…
(more)
▼ Images acquired from magnetic resonance imaging scanners take complex values. The images can be broken into two distinct types of images: magnitude images and phase maps. Magnitude images display structural information while phase maps are
sensitive to magnetic field inhomogeneities and changes in temperature. However, phase maps are discontinuous and a process known as phase unwrapping is needed to remove the discontinuities in the phase map. In this work, a new two dimensional phase
unwrapping algorithm is proposed and results from the proposed algorithm are compared with standard phase unwrapping algorithms. Extensions to the proposed phase unwrapping algorithm are then considered, the proposed two-dimensional phase unwrapping
algorithm is modified and a new thermometry algorithm is presented. Finally, the quantification of contrast agents based on superparamag- netic iron oxide (SPIO) nanoparticles is discussed and a new SPIO quantification algorithm is
proposed.
Subjects/Keywords: Magnetic Resonance Imaging; Diffusion Tensor Imaging; Phase Unwrapping; Positive Contrast; SPIO Quantification; Molecular Imaging
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APA (6th Edition):
Langley, J. A. (2014). Estimation of the phase gradient in MIR. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/27201
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Langley, Jason Allen. “Estimation of the phase gradient in MIR.” 2014. Thesis, University of Georgia. Accessed March 04, 2021.
http://hdl.handle.net/10724/27201.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Langley, Jason Allen. “Estimation of the phase gradient in MIR.” 2014. Web. 04 Mar 2021.
Vancouver:
Langley JA. Estimation of the phase gradient in MIR. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10724/27201.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Langley JA. Estimation of the phase gradient in MIR. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/27201
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
McMaster University
19.
Bilton, Holly A.
THE SYNTHESIS AND EVALUATION OF NEW RADIOPHARMACEUTICALS AND MULTIMODAL IMAGING PROBES.
Degree: PhD, 2019, McMaster University
URL: http://hdl.handle.net/11375/25023
► Technetium-99m (99mTc) radiopharmaceuticals are widely used for diagnostic imaging of heart, kidney, and liver disease, and cancer. Evolution from perfusion type tracers to targeted agents…
(more)
▼ Technetium-99m (99mTc) radiopharmaceuticals are widely used for diagnostic
imaging of heart, kidney, and liver disease, and cancer. Evolution from perfusion type tracers to targeted agents however has proven difficult. 99mTc labeled antibodies for
imaging specific disease biomarkers would be of great interest, however the disparity between the isotopes half-life (6 hours) and the long circulation time of most antibodies (multiple days) has been a significant barrier. Furthermore, the conjugation of bifunctional 99mTc-chelate complexes to small molecules often has a detrimental impact on targeting. The use of bioorthogonal chemistry derived from tetrazines and trans-cyclooctene derivatives, along with pretargeting has the potential to overcome these issues and create a new generation of targeted 99mTc radiopharmaceuticals.
Initially, the synthesis of three generations of imidazole based tridentate chelates linked to a tetrazine was completed. These new ligands were labeled with 99mTc under mild conditions (60 °C, 20 min, pH 3.5) with modest to good radiochemical yields ranging from 31 to 83%. Biodistribution studies revealed that compound 14, which contains a polyethylene glycol 5 (PEG5) linker had the best clearance from non-target tissues. Compound 14 was also used successfully in a pretargeting strategy along with a transcyclooctene (TCO) derivative of the bone targeting bisphosphonate, alendronate (ALN). One hour following the administration of TCO-ALN to BALB/c mice, compound 14 was injected intravenously where uptake at sites of high calcium turn over (i.e. the joints) was observed. At 6 hours post injection, for example, uptake reached as high as 20.1 ± 4.91 and 16.1 ± 4.84 %ID/g in the knee and shoulder, respectively.
Pretargeted
imaging studies were performed subsequently with a TCO-functionalized huA33 antibody in mice bearing SW122 xenografts. The TCO-huA33 antibody was injected 24 hours before the administration of two radiolabeled tetrazines at high and low specific activities. At 6 hours post injection tumour uptake was minimal, with tumour: blood ratios <1 in all cases. Blood clearance studies determined that the tetrazines were being cleared rapidly, with a blood residence half-life of 1.3-2.1 minutes. The hypothesis is that the low concentration of the antibody (owing to its high
molecular weight), combined with the rapid clearance of the tetrazine and significant off-target uptake resulted in unfavorable kinetics and low tumor binding.
Studies of the clearance pathway of 14 were investigated with clinically approved hepatobiliary transport inhibitors to help understand the mechanism of clearance, which could in turn be used to optimize the pharmacokinetics of the tetrazine ligands. A range of different inhibitors of key clearance pathways were evaluated with limited success. However, co-administration of 14 with ALN resulted in a 75% decrease in gall bladder uptake of 14 (216 ± 75.9 to 33.6 ± 3.93 %ID/g). Pretargeting studies of 14 with TCO-ALN in the presence of excess ALN revealed that…
Advisors/Committee Members: Valliant, John F, Chemistry and Chemical Biology.
Subjects/Keywords: Radiopharmaceuticals; Chemistry; Chemical Biology; Technetium-99m; Bioorthogonal Chemistry; Multimodal Imaging; Molecular Imaging; Pretargeted Imaging
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APA (6th Edition):
Bilton, H. A. (2019). THE SYNTHESIS AND EVALUATION OF NEW RADIOPHARMACEUTICALS AND MULTIMODAL IMAGING PROBES. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/25023
Chicago Manual of Style (16th Edition):
Bilton, Holly A. “THE SYNTHESIS AND EVALUATION OF NEW RADIOPHARMACEUTICALS AND MULTIMODAL IMAGING PROBES.” 2019. Doctoral Dissertation, McMaster University. Accessed March 04, 2021.
http://hdl.handle.net/11375/25023.
MLA Handbook (7th Edition):
Bilton, Holly A. “THE SYNTHESIS AND EVALUATION OF NEW RADIOPHARMACEUTICALS AND MULTIMODAL IMAGING PROBES.” 2019. Web. 04 Mar 2021.
Vancouver:
Bilton HA. THE SYNTHESIS AND EVALUATION OF NEW RADIOPHARMACEUTICALS AND MULTIMODAL IMAGING PROBES. [Internet] [Doctoral dissertation]. McMaster University; 2019. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/11375/25023.
Council of Science Editors:
Bilton HA. THE SYNTHESIS AND EVALUATION OF NEW RADIOPHARMACEUTICALS AND MULTIMODAL IMAGING PROBES. [Doctoral Dissertation]. McMaster University; 2019. Available from: http://hdl.handle.net/11375/25023
University of Western Ontario
20.
Nasri, Nivin N.
A Genetically-Encoded Reporter for In Vivo Imaging in Deep Tissues.
Degree: 2020, University of Western Ontario
URL: https://ir.lib.uwo.ca/etd/7130
► Introduction. The ability to track cells in living organisms with sensitivity, accuracy and high spatial resolution would revolutionize the way we study disease. Reporter genes…
(more)
▼ Introduction. The ability to track cells in living organisms with sensitivity, accuracy and high spatial resolution would revolutionize the way we study disease. Reporter genes are valuable tools as they encode detectible products, allowing for quantitative “reporting” of cells that express them. Previously, a gene encoding Organic anion-transporting polypeptide 1a1 (Oatp1a1) was established as a magnetic resonance imaging (MRI) reporter based on its ability to take up the paramagnetic contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). Our objective was to assess, characterize and further develop this system for whole-body tracking of cells in vivo. Methods. Cancer cells were engineered to synthetically express Oatp1a1, or Oatp1b3, a closely related human transporter protein. In our first study, T1-weighted images of Oatp1a1-expressing primary tumours in preclinical animals were acquired before and after administration of 0.1-mmol/kg Gd-EOB-DTPA at 3-Tesla. At endpoint, heterogenous contrast enhancement patterns within the primary tumour architecture were compared to whole-tumour fluorescent histology. In the next study, T1-weighted images of Oatp1b3-expressing primary tumours, and their spontaneous metastases to the lymph nodes and lungs, were acquired before and after administration of 1-mmol/kg Gd-EOB-DTPA at 3-Tesla. In the final study, the feasibility of Oatp1b3 as a photoacoustic reporter gene was assessed by acquiring full-spectrum near infrared photoacoustic images of primary tumours in preclinical animals before and after administration of 8-mg/kg indocyanine green. Results. We were able to demonstrate the feasibility of imaging cancer cells with Oatp1a1 at 3-Tesla and 0.1 mmol/kg Gd-EOB-DTPA. Importantly, as primary tumours grew over time, heterogeneous contrast enhancement patterns that emerged near-endpoint strongly correlated to viable cell distributions on whole-tumour histology. Oatp1b3 was also shown to operate as a MRI reporter gene at 3-Tesla, based on the same principle as Oatp1a1. Impressively, single lymph node metastases and the formation of micrometastases in the lungs of preclinical animals were detected with Oatp1b3-MRI. Finally, we also demonstrated the ability of Oatp1b3 to operate as a photoacoustic reporter gene based on its ability to take up indocyanine green. Conclusion. The Oatp1 reporter gene system is a versatile imaging tool for longitudinal tracking of engineered cells in vivo with sensitivity, high resolution, and 3-dimensional spatial information.
Subjects/Keywords: cellular tracking; magnetic resonance imaging; molecular imaging; Oatp1; photoacoustic imaging; reporter gene; Biotechnology
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APA (6th Edition):
Nasri, N. N. (2020). A Genetically-Encoded Reporter for In Vivo Imaging in Deep Tissues. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/7130
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Nasri, Nivin N. “A Genetically-Encoded Reporter for In Vivo Imaging in Deep Tissues.” 2020. Thesis, University of Western Ontario. Accessed March 04, 2021.
https://ir.lib.uwo.ca/etd/7130.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Nasri, Nivin N. “A Genetically-Encoded Reporter for In Vivo Imaging in Deep Tissues.” 2020. Web. 04 Mar 2021.
Vancouver:
Nasri NN. A Genetically-Encoded Reporter for In Vivo Imaging in Deep Tissues. [Internet] [Thesis]. University of Western Ontario; 2020. [cited 2021 Mar 04].
Available from: https://ir.lib.uwo.ca/etd/7130.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Nasri NN. A Genetically-Encoded Reporter for In Vivo Imaging in Deep Tissues. [Thesis]. University of Western Ontario; 2020. Available from: https://ir.lib.uwo.ca/etd/7130
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Washington University in St. Louis
21.
Solomon, Metasebya.
Video-Rate Fluorescence Molecular Tomography for Hand-held and Multimodal Molecular Imaging.
Degree: PhD, Biomedical Engineering, 2012, Washington University in St. Louis
URL: https://openscholarship.wustl.edu/etd/1019
► In the United States, cancer is the second leading cause of death following heart disease. Although, a variety of treatment regimens are available, cancer…
(more)
▼ In the United States, cancer is the second leading cause of death following heart disease. Although, a variety of treatment regimens are available, cancer management is complicated by the complexity of the disease and the variability, between people, of disease progression and response to therapy. Therefore, advancements in the methods and technologies for cancer diagnosis, prognosis and therapeutic monitoring are critical to improving the treatment of cancer patients. The development of improved
imaging methods for early diagnosis of cancer and of near real-time monitoring of tumor response to therapy may improve outcomes as well as the quality of life of cancer patients. In the last decade,
imaging methods including ultrasound, computed tomography: CT), magnetic resonance
imaging: MRI), single photon emission computed tomography: SPECT), and positron emission tomography: PET), have revolutionized oncology. More recently optical techniques, that have access to unique
molecular reporting strategies and functional contrasts, show promise for oncologic
imaging This dissertation focuses on the development and optimization of a fiber-based, video-rate fluorescence
molecular tomography: FMT) instrument. Concurrent acquisition of fluorescence and reference signals allowed the efficient generation of ratio-metric data for 3D image reconstruction. Accurate depth localization and high sensitivity to fluorescent targets were established to depths of >10 mm. In vivo accumulation of indocyanine green dye was imaged in the region of the sentinel lymph node: SLN) following intradermal injection into the forepaw of rats. These results suggest that video-rate FMT has potential as a clinical tool for noninvasive mapping of SLN. Spatial and temporal co-registration of nuclear and optical images can enable the fusion of the information from these complementary
molecular imaging modalities. A critical challenge is in integrating the optical and nuclear
imaging hardware. Flexible fiber-based FMT systems provide a viable solution. The various
imaging bore sizes of small animal nuclear
imaging systems can potentially accommodate the FMT fiber
imaging arrays. In addition FMT
imaging facilitates co-registering the nuclear and optical contrasts in time. In this dissertation, the feasibility of integrating the fiber-based, video-rate FMT system with a commercial preclinical NanoSPECT/CT platform was established. Feasibility of in vivo
imaging is demonstrated by tracking a monomolecular multimodal-
imaging agent: MOMIA) during transport from the forepaw to the axillary lymph nodes region of a rat. These co-registered FMT/SPECT/CT
imaging results with MOMIAs may facilitate the development of the next generation preclinical and clinical multimodal optical-nuclear platforms for a broad array of
imaging applications, and help elucidate the underlying biological processes relevant to cancer diagnosis and therapy monitoring. Finally, I demonstrated that video-rate FMT is sufficiently fast to enable
imaging of cardiac,…
Advisors/Committee Members: Samuel Achilefu.
Subjects/Keywords: Diffuse Optical Tomography; Fluorescence Molecular Tomography; Lymph Node Imaging; Multimodal Imaging; Small Animal Imaging
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APA (6th Edition):
Solomon, M. (2012). Video-Rate Fluorescence Molecular Tomography for Hand-held and Multimodal Molecular Imaging. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/etd/1019
Chicago Manual of Style (16th Edition):
Solomon, Metasebya. “Video-Rate Fluorescence Molecular Tomography for Hand-held and Multimodal Molecular Imaging.” 2012. Doctoral Dissertation, Washington University in St. Louis. Accessed March 04, 2021.
https://openscholarship.wustl.edu/etd/1019.
MLA Handbook (7th Edition):
Solomon, Metasebya. “Video-Rate Fluorescence Molecular Tomography for Hand-held and Multimodal Molecular Imaging.” 2012. Web. 04 Mar 2021.
Vancouver:
Solomon M. Video-Rate Fluorescence Molecular Tomography for Hand-held and Multimodal Molecular Imaging. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2012. [cited 2021 Mar 04].
Available from: https://openscholarship.wustl.edu/etd/1019.
Council of Science Editors:
Solomon M. Video-Rate Fluorescence Molecular Tomography for Hand-held and Multimodal Molecular Imaging. [Doctoral Dissertation]. Washington University in St. Louis; 2012. Available from: https://openscholarship.wustl.edu/etd/1019
University of Texas – Austin
22.
Luke, Geoffrey Patrick.
Functional and molecular photoacoustic imaging for the detection of lymph node metastasis.
Degree: PhD, Electrical and Computer Engineering, 2013, University of Texas – Austin
URL: http://hdl.handle.net/2152/28713
► Accurate detection of the spread of cancer is critical for planning the best treatment strategy for a patient. Currently, an invasive sentinel lymph node biopsy…
(more)
▼ Accurate detection of the spread of cancer is critical for planning the best treatment strategy for a patient. Currently, an invasive sentinel lymph node biopsy is commonly used to detect metastases after a primary tumor is detected. This procedure results in patient morbidity, requires weeks of waiting, and is prone to sampling error. This dissertation presents new developments in an emerging biomedical
imaging modality – photoacoustic
imaging – and their application to improving the detection of metastases in the lymphatic system in a metastatic mouse model of squamous cell carcinoma of the oral cavity. Label-free spectroscopic photoacoustic
imaging is demonstrated to detect hypoxia that results from the development of sub-millimeter cancer foci in the lymph node. In order to improve the sensitivity to micrometastases, molecularly-activated plasmonic nanosensers which are targeted to the epidermal growth factor receptor are introduced. The nanosensors are demonstrated to detect metastases consisting of only a few tens of cells. Improvements to spectroscopic photoacoustic
imaging are then demonstrated by selecting
imaging wavelengths based on the spectral properties of the optical absorbers. Finally, a new contrast agent – silica-coated gold nanoplates – are used to map the sentinel lymph node with high contrast. The final result is a set of tools that can be used to noninvasively detect micrometastases and improve
molecular photoacoustic
imaging.
Advisors/Committee Members: Emelianov, Stanislav Y. (advisor).
Subjects/Keywords: Photoacoustic imaging; Molecular imaging; Sentinel lymph node; Ultrasound imaging; Nanoparticles; Image processing; Spectroscopy
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APA (6th Edition):
Luke, G. P. (2013). Functional and molecular photoacoustic imaging for the detection of lymph node metastasis. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/28713
Chicago Manual of Style (16th Edition):
Luke, Geoffrey Patrick. “Functional and molecular photoacoustic imaging for the detection of lymph node metastasis.” 2013. Doctoral Dissertation, University of Texas – Austin. Accessed March 04, 2021.
http://hdl.handle.net/2152/28713.
MLA Handbook (7th Edition):
Luke, Geoffrey Patrick. “Functional and molecular photoacoustic imaging for the detection of lymph node metastasis.” 2013. Web. 04 Mar 2021.
Vancouver:
Luke GP. Functional and molecular photoacoustic imaging for the detection of lymph node metastasis. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2013. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2152/28713.
Council of Science Editors:
Luke GP. Functional and molecular photoacoustic imaging for the detection of lymph node metastasis. [Doctoral Dissertation]. University of Texas – Austin; 2013. Available from: http://hdl.handle.net/2152/28713
Rochester Institute of Technology
23.
Schug, Nicholas C.
Modular Synthesis of Dual- and Tri-modal Targeted Molecular Imaging Agents.
Degree: MS, School of Chemistry and Materials Science (COS), 2020, Rochester Institute of Technology
URL: https://scholarworks.rit.edu/theses/10424
► There are few reported methods for combining two or three different imaging dyes, metals, or dye-metal combinations, followed by the conjugation of a disease-…
(more)
▼ There are few reported methods for combining two or three different
imaging dyes, metals, or dye-metal combinations, followed by the conjugation of a disease- targeting group to enable the use a given
imaging system for multiple
imaging applications. Previously, peptides have been used as scaffolds for dyes and metals used in diagnostic techniques such as optical
molecular imaging (OMI), positron emission tomography (PET), and magnetic resonance
imaging (MRI). The aim of this project was to reassemble peptide-based
imaging agents through a modular method by coupling together modules comprised of amino acids with
imaging agents attached to their side chains to form “
imaging peptides,” followed by attaching a cancer-targeting group in the final step. This new modular approach for the synthesis of a diverse set of targeted
molecular imaging agents (TMIAs) was optimized and exemplified by the synthesis of dual modal PET-MRI, dual OMI-MRI and dual metal (di-gadolinium for MRI), and the partial synthesis of a tri-modal OMI-PET-MRI agent. The dual modal
imaging peptides were conjugated through a linker to targeting groups for lung cancer (A549 cells) and prostate cancer (PSMA positive C4-2) cells. In addition to
imaging applications for early detection, active surveillance, image guided biopsies and surgery, this modular approach could potentially be used for creating therapeutic agents to treat cancer patients.
Advisors/Committee Members: Hans Schmitthenner.
Subjects/Keywords: Cancer detection; Imaging agents; Molecular imaging; MRI; PET
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APA (6th Edition):
Schug, N. C. (2020). Modular Synthesis of Dual- and Tri-modal Targeted Molecular Imaging Agents. (Masters Thesis). Rochester Institute of Technology. Retrieved from https://scholarworks.rit.edu/theses/10424
Chicago Manual of Style (16th Edition):
Schug, Nicholas C. “Modular Synthesis of Dual- and Tri-modal Targeted Molecular Imaging Agents.” 2020. Masters Thesis, Rochester Institute of Technology. Accessed March 04, 2021.
https://scholarworks.rit.edu/theses/10424.
MLA Handbook (7th Edition):
Schug, Nicholas C. “Modular Synthesis of Dual- and Tri-modal Targeted Molecular Imaging Agents.” 2020. Web. 04 Mar 2021.
Vancouver:
Schug NC. Modular Synthesis of Dual- and Tri-modal Targeted Molecular Imaging Agents. [Internet] [Masters thesis]. Rochester Institute of Technology; 2020. [cited 2021 Mar 04].
Available from: https://scholarworks.rit.edu/theses/10424.
Council of Science Editors:
Schug NC. Modular Synthesis of Dual- and Tri-modal Targeted Molecular Imaging Agents. [Masters Thesis]. Rochester Institute of Technology; 2020. Available from: https://scholarworks.rit.edu/theses/10424
McMaster University
24.
Zlitni, Aimen.
The Development and Evaluation of Multi-Modal Microbubbles and New Strategies for Targeted Ultrasound, Nuclear and Optical Imaging.
Degree: PhD, 2016, McMaster University
URL: http://hdl.handle.net/11375/19578
► Gas filled microbubbles (MBs) stabilized by a shell (e.g. lipids) are commonly used as ultrasound (US) contrast agents. Attaching biomolecules to the surface of MBs…
(more)
▼ Gas filled microbubbles (MBs) stabilized by a shell (e.g. lipids) are commonly used as ultrasound (US) contrast agents. Attaching biomolecules to the surface of MBs allows for molecular US imaging of various diseases. With the increased interest in targeted US imaging, new platforms to prepare disease-targeted MBs are necessary. Furthermore, attaching signaling agents to MBs creates multi-modal imaging opportunities, enhancing visualization and quantification of disease biomarkers.
In this thesis, MBs labeled with 99mTc and/or rhodamine dye by taking advantage of the strong interaction between biotin and streptavidin are reported. Radiolabeling of MBs was achieved in good radiochemical yield (~ 30%). 99mTc-labeled MBs were targeted to vascular endothelial growth factor receptor 2 (VEGFR2) using an anti-VEGFR2 antibody and to prostate specific membrane antigen (PSMA) using small-molecule based PSMA inhibitors. In vitro evaluations showed successful binding of MBs to the target while in vivo targeting assessments were unsuccessful.
New strategies to target MBs to the site of interest were then developed through the use of the bioorthogonal reaction between tetrazine (Tz) and trans-cyclooctene (TCO). A biotinylated derivative of Tz was loaded on streptavidin coated MBs to create a Tz-derivatized MB (MBTz). Targeting MBTz to extracellular markers of cancer such as VEGFR2, PSMA and urokinase plasminogen activator receptor (uPAR) in vitro was achieved using TCO-conjugated antibodies. In vivo targeting was successful for VEGFR2 and PSMA, but not uPAR.
Translating the new strategy to other US contrast agents was then investigated. Gas vesicles (GVs) produced in halobacteria were conjugated with TCO using amide-coupling chemistry. A 99mTc-labeled derivative of Tz was loaded on TCO-GVs (RCY= 59%) and their distribution assessed by SPECT/CT imaging and ex vivo tissue counting. Having established a convenient platform to conjugate molecules to GVs and MBs, future work focuses on developing a new generation of human compatible molecular US imaging probes.
Dissertation
Doctor of Philosophy (PhD)
Advisors/Committee Members: Valliant, John, Chemical Biology.
Subjects/Keywords: Multimodal imaging; Molecular ultrasound imaging of cancer; Microbubbles; bioorthogonal chemistry
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APA (6th Edition):
Zlitni, A. (2016). The Development and Evaluation of Multi-Modal Microbubbles and New Strategies for Targeted Ultrasound, Nuclear and Optical Imaging. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/19578
Chicago Manual of Style (16th Edition):
Zlitni, Aimen. “The Development and Evaluation of Multi-Modal Microbubbles and New Strategies for Targeted Ultrasound, Nuclear and Optical Imaging.” 2016. Doctoral Dissertation, McMaster University. Accessed March 04, 2021.
http://hdl.handle.net/11375/19578.
MLA Handbook (7th Edition):
Zlitni, Aimen. “The Development and Evaluation of Multi-Modal Microbubbles and New Strategies for Targeted Ultrasound, Nuclear and Optical Imaging.” 2016. Web. 04 Mar 2021.
Vancouver:
Zlitni A. The Development and Evaluation of Multi-Modal Microbubbles and New Strategies for Targeted Ultrasound, Nuclear and Optical Imaging. [Internet] [Doctoral dissertation]. McMaster University; 2016. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/11375/19578.
Council of Science Editors:
Zlitni A. The Development and Evaluation of Multi-Modal Microbubbles and New Strategies for Targeted Ultrasound, Nuclear and Optical Imaging. [Doctoral Dissertation]. McMaster University; 2016. Available from: http://hdl.handle.net/11375/19578
McMaster University
25.
Tao, Ashley T.
Advanced Methods in Molecular Breast Imaging.
Degree: PhD, 2016, McMaster University
URL: http://hdl.handle.net/11375/19900
► Molecular breast imaging (MBI) is a relatively new clinical breast imaging modality, which has the potential to have a significant impact in breast cancer screening…
(more)
▼ Molecular breast imaging (MBI) is a relatively new clinical breast imaging modality, which has the potential to have a significant impact in breast cancer screening and perioperative breast imaging for women with high risk factors for developing breast cancer. Two objectives were proposed in this thesis to increase the use of MBI. First, a magnetic resonance (MR)-compatible gamma camera was developed for combined molecular/MR breast imaging. MBI is a functional imaging technique with high specificity and sensitivity but could benefit from the addition of anatomical information from breast MRI for lesion localization, cancer staging, treatment planning and monitoring. A small area (8cm x 8cm) cadmium zinc telluride (CZT) based gamma camera was developed and tested for MR compatibility in both sequential and simultaneous imaging conditions. Results indicated that the gamma camera was minimally affected during both sequential and simultaneous imaging with a gradient echo (GRE) and spoiled gradient echo (GRE) sequence. Signal to noise ratio (SNR) degradation was observed in the MR images but no geometric distortions were observed. Simultaneous imaging is feasible, but a reassessment of the RF shielding would be required to minimize the noise contribution degrading image quality. Second, backscatter photons were investigated as a potential dose reduction technique for MBI. While the effective dose from MBI is relatively low in comparison to other nuclear medicine procedures, the dose is considered high in relation to mammography and in order to increase acceptance as an alternative breast imaging method, dose reduction is an important objective. Backscatter photons have the same spatial information as primary photons but are typically discarded along with other scattered photons. A scatter compensation method called the triple energy window (TEW) was used to extract backscatter photons from the Compton scattering spectrum and added to the primary photons, increasing count sensitivity by 6%. The noise level matched the increase in contrast leading to negligible change in lesion contrast to noise ratio (CNR). Dose reduction is not justified with this particular technique because of the elevated noise level, but the use of backcsatter photons show potential with improved contrast.
Dissertation
Doctor of Philosophy (PhD)
Advisors/Committee Members: Farncombe, Troy H., Medical Physics.
Subjects/Keywords: Molecular breast imaging; MRI; Nuclear medicine; Dual-modality imaging; Backscatter
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APA (6th Edition):
Tao, A. T. (2016). Advanced Methods in Molecular Breast Imaging. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/19900
Chicago Manual of Style (16th Edition):
Tao, Ashley T. “Advanced Methods in Molecular Breast Imaging.” 2016. Doctoral Dissertation, McMaster University. Accessed March 04, 2021.
http://hdl.handle.net/11375/19900.
MLA Handbook (7th Edition):
Tao, Ashley T. “Advanced Methods in Molecular Breast Imaging.” 2016. Web. 04 Mar 2021.
Vancouver:
Tao AT. Advanced Methods in Molecular Breast Imaging. [Internet] [Doctoral dissertation]. McMaster University; 2016. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/11375/19900.
Council of Science Editors:
Tao AT. Advanced Methods in Molecular Breast Imaging. [Doctoral Dissertation]. McMaster University; 2016. Available from: http://hdl.handle.net/11375/19900
University of Toronto
26.
Philp, Lauren.
Towards Clinical Translation of the Porphysome: Establishment of Endometrial Cancer Applications and Investigation of Metabolic Differences in Pyrolipid Isomers.
Degree: 2018, University of Toronto
URL: http://hdl.handle.net/1807/91426
► Treatment of endometrial cancer consists of surgery ± adjuvant therapy depending on lymph node involvement determined by lymphadenectomy. Targeting lymphadenectomy to patients with known metastases…
(more)
▼ Treatment of endometrial cancer consists of surgery ± adjuvant therapy depending on lymph node involvement determined by lymphadenectomy. Targeting lymphadenectomy to patients with known metastases would provide diagnostic and therapeutic benefits while reducing morbidity. Porphysomes are self-assembling nanoparticles made from a multifunctional porphyrin-lipid monomer (pyrolipid) which accumulate preferentially in malignant tissue. Pyrolipid is created through an acylation reaction during which isomerization can occur. A VX2 model of endometrial cancer with retroperitoneal metastases was used to investigate the accuracy of pre-operative 64Cu-Porphysome-enabled PET imaging of lymph nodes and the sensitivity / specificity of in-vivo porphyrin-fluorescence image-guided lymphadenectomy. Pharmacokinetic, biodistribution and biodegradation studies were used to determine differences in Sn1 and Sn2 isomeric Porphysomes. This study demonstrated that Porphysomes are a highly sensitive imaging tool to diagnose primary tumour, metastatic lymph nodes and intra-abdominal metastases and that Sn2 pyrolipid is the optimal isomer for clinical translation due to the preferential biodegradation profile.
M.Sc.
Advisors/Committee Members: Bernardini, Marcus Q, Medical Science.
Subjects/Keywords: Endometrial Cancer; Fluorescence Imaging; Lymphadenectomy; Metastasis; Molecular Imaging; Nanoparticle; 0574
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APA (6th Edition):
Philp, L. (2018). Towards Clinical Translation of the Porphysome: Establishment of Endometrial Cancer Applications and Investigation of Metabolic Differences in Pyrolipid Isomers. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/91426
Chicago Manual of Style (16th Edition):
Philp, Lauren. “Towards Clinical Translation of the Porphysome: Establishment of Endometrial Cancer Applications and Investigation of Metabolic Differences in Pyrolipid Isomers.” 2018. Masters Thesis, University of Toronto. Accessed March 04, 2021.
http://hdl.handle.net/1807/91426.
MLA Handbook (7th Edition):
Philp, Lauren. “Towards Clinical Translation of the Porphysome: Establishment of Endometrial Cancer Applications and Investigation of Metabolic Differences in Pyrolipid Isomers.” 2018. Web. 04 Mar 2021.
Vancouver:
Philp L. Towards Clinical Translation of the Porphysome: Establishment of Endometrial Cancer Applications and Investigation of Metabolic Differences in Pyrolipid Isomers. [Internet] [Masters thesis]. University of Toronto; 2018. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1807/91426.
Council of Science Editors:
Philp L. Towards Clinical Translation of the Porphysome: Establishment of Endometrial Cancer Applications and Investigation of Metabolic Differences in Pyrolipid Isomers. [Masters Thesis]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/91426
Delft University of Technology
27.
Ivashchenko, O.
Development and applications of high-performance small-animal SPECT.
Degree: 2017, Delft University of Technology
URL: http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb
;
urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb
;
3fb5d84e-39ee-43e8-87c6-21871900dabb
;
10.4233/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb
;
urn:isbn:978-94-92516-35-0
;
urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb
;
http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb
Subjects/Keywords: SPECT; preclinical imaging; molecular imaging
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APA (6th Edition):
Ivashchenko, O. (2017). Development and applications of high-performance small-animal SPECT. (Doctoral Dissertation). Delft University of Technology. Retrieved from http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; 3fb5d84e-39ee-43e8-87c6-21871900dabb ; 10.4233/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; urn:isbn:978-94-92516-35-0 ; urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb
Chicago Manual of Style (16th Edition):
Ivashchenko, O. “Development and applications of high-performance small-animal SPECT.” 2017. Doctoral Dissertation, Delft University of Technology. Accessed March 04, 2021.
http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; 3fb5d84e-39ee-43e8-87c6-21871900dabb ; 10.4233/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; urn:isbn:978-94-92516-35-0 ; urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb.
MLA Handbook (7th Edition):
Ivashchenko, O. “Development and applications of high-performance small-animal SPECT.” 2017. Web. 04 Mar 2021.
Vancouver:
Ivashchenko O. Development and applications of high-performance small-animal SPECT. [Internet] [Doctoral dissertation]. Delft University of Technology; 2017. [cited 2021 Mar 04].
Available from: http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; 3fb5d84e-39ee-43e8-87c6-21871900dabb ; 10.4233/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; urn:isbn:978-94-92516-35-0 ; urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb.
Council of Science Editors:
Ivashchenko O. Development and applications of high-performance small-animal SPECT. [Doctoral Dissertation]. Delft University of Technology; 2017. Available from: http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; 3fb5d84e-39ee-43e8-87c6-21871900dabb ; 10.4233/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; urn:isbn:978-94-92516-35-0 ; urn:NBN:nl:ui:24-uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb ; http://resolver.tudelft.nl/uuid:3fb5d84e-39ee-43e8-87c6-21871900dabb
University of Washington
28.
Kang, Soyoung.
Investigation of biomarker-targeted SERS nanoparticles for multiplexed molecular imaging of fresh tissue specimens.
Degree: PhD, 2018, University of Washington
URL: http://hdl.handle.net/1773/42476
► Biomarker-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have been explored as a viable option for targeting and imaging multiple cell-surface protein biomarkers of cancer. A…
(more)
▼ Biomarker-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have been explored as a viable option for targeting and
imaging multiple cell-surface protein biomarkers of cancer. A previously-developed Raman-encoded
molecular imaging (REMI) technique utilizes such targeted NPs for topical application onto excised tissues to enable rapid visualization of a multiplexed panel of cell surface biomarkers at surgical margin surfaces. While it has been demonstrated that REMI may potentially be used to guide tumor-resection procedures, the strategy would benefit from improvements described in this thesis. First, an investigation into channel-compressed spectrometry revealed that up to 64 times fewer spectral channels may be used to accurately demultiplex up to five SERS NP flavors (compared to our previous methods). This strategy offers the potential for improved
imaging speed and/or detection sensitivity with a low-channel count detector in future REMI systems. Next, the complexities in nonspecific accumulation, diffusion, and chemical binding of targeted NPs in fresh tissues were explored in a microscopic investigation quantifying the specific vs. nonspecific accumulation of topically-applied NPs as they diffuse into fresh tissue. The findings from this study led us to hypothesize and later demonstrate that by reducing NP diffusion, nonspecific accumulations of NPs in tissue is reduced, thereby allowing for
molecular imaging of fresh tissue surfaces with higher NP ratios (targeted vs. untargeted), and that the staining can be achieved more rapidly than before (6-min topical application). A third, and final, study is presented, to help establish optimized protocols for the staining and rinsing of fresh tissue specimens for REMI using a mathematical model that incorporates multi-layer diffusion in addition to binding and nonspecific retention compartments. The goal of this final study is for this forward model to ultimately be used to enable quantitative methods of evaluating
molecular expression, which could enable improved assessments of tumor margins (e.g., the use of multi-stage staining/rinsing processes to allow kinetic model fitting of data). In summary, the first two studies enable the design of more rapid
molecular imaging systems, and NP agents with improved sensitivity and contrast, respectively, for rapid
molecular imaging of fresh tissues suitable for intraoperative clinical settings. The mathematical model study is valuable for accurately quantifying biomarker expression levels to potentially increase the sensitivity and specificity of tumor detection at surgical margins.
Advisors/Committee Members: Liu, Jonathan T.C. (advisor).
Subjects/Keywords: molecular imaging; multiplexed molecular imaging; nanoparticles; optics; Raman spectroscopy; surface-enhanced Raman scattering; Medical imaging; Optics; Mechanical engineering; Mechanical engineering
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Export
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APA (6th Edition):
Kang, S. (2018). Investigation of biomarker-targeted SERS nanoparticles for multiplexed molecular imaging of fresh tissue specimens. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/42476
Chicago Manual of Style (16th Edition):
Kang, Soyoung. “Investigation of biomarker-targeted SERS nanoparticles for multiplexed molecular imaging of fresh tissue specimens.” 2018. Doctoral Dissertation, University of Washington. Accessed March 04, 2021.
http://hdl.handle.net/1773/42476.
MLA Handbook (7th Edition):
Kang, Soyoung. “Investigation of biomarker-targeted SERS nanoparticles for multiplexed molecular imaging of fresh tissue specimens.” 2018. Web. 04 Mar 2021.
Vancouver:
Kang S. Investigation of biomarker-targeted SERS nanoparticles for multiplexed molecular imaging of fresh tissue specimens. [Internet] [Doctoral dissertation]. University of Washington; 2018. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1773/42476.
Council of Science Editors:
Kang S. Investigation of biomarker-targeted SERS nanoparticles for multiplexed molecular imaging of fresh tissue specimens. [Doctoral Dissertation]. University of Washington; 2018. Available from: http://hdl.handle.net/1773/42476
University of Toronto
29.
Burgess, Allysa Jane Laura.
Topical Molecular Beacons for In Vivo Image-guided Resection of Oral Carcinoma.
Degree: 2014, University of Toronto
URL: http://hdl.handle.net/1807/67951
► Oral carcinoma has become a major health problem, with nearly 300,000 people diagnosed worldwide annually. The 5-year survival rate is as low as 30%, mainly…
(more)
▼ Oral carcinoma has become a major health problem, with nearly 300,000 people diagnosed worldwide annually. The 5-year survival rate is as low as 30%, mainly attributed to poor delineation of lesions. Optical imaging approaches to identify oral carcinoma tissue during surgery are currently in trial. While decreased recurrence rates are shown, high rates of false positives occur. Expanding upon this, a molecular beacon strategy for oral carcinoma delineation was devised.The selected MMP molecular beacon consists of a fluorophore conjugated to a quencher via a disease-specific linker, activated by MMPs. The activated beacon becomes fluorescent, guiding resection. MMPs have been associated with oral tumors and several members as highly upregulated in oral carcinoma, making them an ideal target.I investigated, in vivo, the utility of this MMP-cleavable beacon in targeting oral carcinoma. Here I demonstrate its high tumor specificity and potential for integration into the clinic to improve patient outcome.
M.Sc.
Advisors/Committee Members: Zheng, Gang, Medical Biophysics.
Subjects/Keywords: matrix metalloproteinases; molecular beacons; molecular imaging; oral carcinoma; 0786
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APA (6th Edition):
Burgess, A. J. L. (2014). Topical Molecular Beacons for In Vivo Image-guided Resection of Oral Carcinoma. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/67951
Chicago Manual of Style (16th Edition):
Burgess, Allysa Jane Laura. “Topical Molecular Beacons for In Vivo Image-guided Resection of Oral Carcinoma.” 2014. Masters Thesis, University of Toronto. Accessed March 04, 2021.
http://hdl.handle.net/1807/67951.
MLA Handbook (7th Edition):
Burgess, Allysa Jane Laura. “Topical Molecular Beacons for In Vivo Image-guided Resection of Oral Carcinoma.” 2014. Web. 04 Mar 2021.
Vancouver:
Burgess AJL. Topical Molecular Beacons for In Vivo Image-guided Resection of Oral Carcinoma. [Internet] [Masters thesis]. University of Toronto; 2014. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1807/67951.
Council of Science Editors:
Burgess AJL. Topical Molecular Beacons for In Vivo Image-guided Resection of Oral Carcinoma. [Masters Thesis]. University of Toronto; 2014. Available from: http://hdl.handle.net/1807/67951
University of California – San Francisco
30.
Darragh, Molly Rose.
Targeting the Active Serine Protease MT-SP1 for Tumor Detection <italics>in vivo</italics>.
Degree: Biophysics, 2010, University of California – San Francisco
URL: http://www.escholarship.org/uc/item/69q0228b
► Cancer is a disease which develops as the result of many negative changes in the biology of otherwise healthy tissue. Non-invasive imaging of aberrant, tumor-associated…
(more)
▼ Cancer is a disease which develops as the result of many negative changes in the biology of otherwise healthy tissue. Non-invasive imaging of aberrant, tumor-associated molecules or processes can be used to isolate and characterize the malignancy, but first one must identify those characteristics which differentiate normal and cancerous tissues. Proteases are associated with cancer growth and progression and are often considered in the search for biomarkers to be used in tumor detection and evaluation. Membrane-Type Serine Protease 1 (MT-SP1) is a membrane anchored protease which is upregulated in epithelial cancers. A dysregulation in MT-SP1/matriptase levels with respect to its cognate inhibitor hepatocyte growth factor activator inhibitor-1 [HAI-1] suggests that it is an increase in proteolytic activity that significantly differentiates malignant from normal tissue. The Craik lab has developed antibodies which bind to and inhibit MT-SP1, but the utility of these probes, and of MT-SP1 activity as a cancer-associated biomarker, has yet to be established. Here we show that these antibodies inhibit the full-length protein on the surface of cancer cells and that they may be functionalized for imaging of this activity <italics>in vivo</italics>. The antibodies were first used to target and inhibit MT-SP1 on human cancer cell lines which express MT-SP1 mRNA. This activity was then targeted <italics>in vivo</italics> using xenograft mouse models of cancer. It was found that the antibodies preferentially localize to tumors which express MT-SP1, suggesting that MT-SP1 activity is a novel biomarker for epithelial cancer and these antibodies provide a non-invasive method for detecting this activity <italics>in vivo</italics>.
Subjects/Keywords: Biology, Molecular; Cancer; Matriptase; Molecular Imaging; Protease; Protease Activity
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APA (6th Edition):
Darragh, M. R. (2010). Targeting the Active Serine Protease MT-SP1 for Tumor Detection <italics>in vivo</italics>. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/69q0228b
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Darragh, Molly Rose. “Targeting the Active Serine Protease MT-SP1 for Tumor Detection <italics>in vivo</italics>.” 2010. Thesis, University of California – San Francisco. Accessed March 04, 2021.
http://www.escholarship.org/uc/item/69q0228b.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Darragh, Molly Rose. “Targeting the Active Serine Protease MT-SP1 for Tumor Detection <italics>in vivo</italics>.” 2010. Web. 04 Mar 2021.
Vancouver:
Darragh MR. Targeting the Active Serine Protease MT-SP1 for Tumor Detection <italics>in vivo</italics>. [Internet] [Thesis]. University of California – San Francisco; 2010. [cited 2021 Mar 04].
Available from: http://www.escholarship.org/uc/item/69q0228b.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Darragh MR. Targeting the Active Serine Protease MT-SP1 for Tumor Detection <italics>in vivo</italics>. [Thesis]. University of California – San Francisco; 2010. Available from: http://www.escholarship.org/uc/item/69q0228b
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
◁ [1] [2] [3] [4] [5] … [17] ▶
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Open Access Theses and Dissertations