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You searched for +publisher:"University of Arizona" +contributor:("Kuo, Philip H."). Showing records 1 – 3 of 3 total matches.

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University of Arizona

1. Gilmore, Samuel Clyde. The Development of Contrast Agents for PET/MRI and CatalyCEST MRI .

Degree: 2018, University of Arizona

A class of MRI contrast agent, CEST MRI agents, has offered a new paradigm to image physiochemical functions and molecular biomarkers. 125 CEST MRI agents were evaluated regarding concentration, toxicity, saturation power and time, and chemical shift for clinical translation. Small molecule and macromolecule PARACEST agents generate CEST signal using lanthanide metals with low concentrations but high saturation powers and times. LipoCEST agents have lower concentration in vivo with low saturation powers and times. However, the chemical shifts of lipoCEST agents are lower that are similar to DIACEST agents and have toxicity similar to PARACEST agents. Transition metals have lower concentration and higher chemical shifts but these agents have not been assessed in vivo. DIACEST MRI agents using amino acids and metabolites avoid toxicity and concentration issues. These agents overlap with the bulk water signal and have variable saturation powers and times. Glucose, iopamidol, and iopromide have consistency with saturation powers and time with low toxicity but only have been assessed for uptake/metabolism and pH mapping studies. Salicylic acid based agents offer an option for clinical development due to the adaptability to enzyme response with low saturation powers and times. The unknown toxicity and high concentration may slow development for the clinic. We have developed an innovative imaging method, catalyCEST MRI, to detect the activity of reductase enzymes within in vivo mouse tumor models. This methodology creates CEST by selectively saturating the magnetic resonance of a proton on the agent which transfers the saturation effect to water through a chemical exchange. With catalyCEST MRI, the enzyme catalyzes a change in the chemical structure of the agent and the change in CEST is monitored. Additionally, a control CEST signal unresponsive to enzymatic catalysis is also monitored to improve quantitative imaging. We have synthesized a carbamate catalyCEST agent designed to detect nitroreductase activitites. Derived from salicylic acid, this agent has the potential to be translated for clinical studies. This report will present the catalyCEST MRI mechanism for the detection of reductase enzyme activity and progression towards in vivo studies with mouse tumor models. Several Gd3+-based pH-sensitive contrast agents that change T1-weighted MRI contrast have been synthesized but have been limited to in vitro studies. A previously described pH sensitive 4AMP-Gd3+-DOTA contrast agent was utilized to map the extracellular tissue pH in a rat glioma model. Additionally, the 4AMP-Gd3+-DOTA contrast agent has been conjugated with an 18F-fluorine analogue and demonstrated to quantitatively measure pH in phantom models as a bimodal PET/MRI contrast agent. In this study, we describe the synthesis of a 4AMP-Gd3+-DOTA derivative conjugated with FDG through functionalization of an α-amino-DOTA and subsequent glycosylation with commercially-available 18F-FDG. The efficacy of the synthesis route may provide an alternative to the design… Advisors/Committee Members: Pagel, Mark D (advisor), Jewett, John C (advisor), Montfort, William R. (committeemember), Kuo, Philip H. (committeemember).

Subjects/Keywords: CatalyCEST MRI; CEST MRI; Hypoxia Imaging; MRI; PET/MRI; pH Imaging

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APA (6th Edition):

Gilmore, S. C. (2018). The Development of Contrast Agents for PET/MRI and CatalyCEST MRI . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/631327

Chicago Manual of Style (16th Edition):

Gilmore, Samuel Clyde. “The Development of Contrast Agents for PET/MRI and CatalyCEST MRI .” 2018. Doctoral Dissertation, University of Arizona. Accessed October 23, 2019. http://hdl.handle.net/10150/631327.

MLA Handbook (7th Edition):

Gilmore, Samuel Clyde. “The Development of Contrast Agents for PET/MRI and CatalyCEST MRI .” 2018. Web. 23 Oct 2019.

Vancouver:

Gilmore SC. The Development of Contrast Agents for PET/MRI and CatalyCEST MRI . [Internet] [Doctoral dissertation]. University of Arizona; 2018. [cited 2019 Oct 23]. Available from: http://hdl.handle.net/10150/631327.

Council of Science Editors:

Gilmore SC. The Development of Contrast Agents for PET/MRI and CatalyCEST MRI . [Doctoral Dissertation]. University of Arizona; 2018. Available from: http://hdl.handle.net/10150/631327


University of Arizona

2. High, Rachel. Evaluations of pancreatic cancer with acidoCEST MRI .

Degree: 2019, University of Arizona

Pancreatic ductal adenocarcinoma (PDAC) is a virulent disease which readily develops resistances to prevailing chemotherapies. PDAC is often not diagnosed until the disease presents in an inoperable late stage. Early detection of PDAC while there is still hope for effective treatment is critical to survival. Cancer cells experience a metabolic shift towards aerobic glycolysis as they develop. This atypical metabolism results in the production and export of lactic acid, which results in acidification of the extracellular tumor microenvironment. Thus, acidosis is a biomarker of cancer development. Our research program uses a technique called chemical exchange saturation transfer magnetic resonance imaging (acidoCEST MRI) to measure acidosis in the extracellular microenvironment. The work presented in this dissertation will focus on characterization of acidosis in PDAC using acidoCEST MRI. Chapter 1 reviews components of the tumor microenvironment that are affected by acidosis as well as briefly overviews aspects of the microenvironment of pancreatic cancer. Chapter 2 presents work analyzing the role of the glucose transporter GLUT3 in chemoresistance and acidosis of two pancreatic cancer cell lines. Chapter 3 explores the use of acidosis as a prognostic biomarker of pancreatic cancer development. Finally, chapter 4 highlights future studies which would be a natural continuation of the work in this dissertation or would contribute to the advancement of acidoCEST MRI as a research technique. Advisors/Committee Members: Pagel, Mark D (advisor), Barton, Jennifer K (advisor), Heimark, Ronald L. (committeemember), Futscher, Bernard W. (committeemember), Kuo, Philip H. (committeemember).

Subjects/Keywords: acidosis; cancer; MRI; pancreatic; PDAC; pH

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

APA (6th Edition):

High, R. (2019). Evaluations of pancreatic cancer with acidoCEST MRI . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/631951

Chicago Manual of Style (16th Edition):

High, Rachel. “Evaluations of pancreatic cancer with acidoCEST MRI .” 2019. Doctoral Dissertation, University of Arizona. Accessed October 23, 2019. http://hdl.handle.net/10150/631951.

MLA Handbook (7th Edition):

High, Rachel. “Evaluations of pancreatic cancer with acidoCEST MRI .” 2019. Web. 23 Oct 2019.

Vancouver:

High R. Evaluations of pancreatic cancer with acidoCEST MRI . [Internet] [Doctoral dissertation]. University of Arizona; 2019. [cited 2019 Oct 23]. Available from: http://hdl.handle.net/10150/631951.

Council of Science Editors:

High R. Evaluations of pancreatic cancer with acidoCEST MRI . [Doctoral Dissertation]. University of Arizona; 2019. Available from: http://hdl.handle.net/10150/631951


University of Arizona

3. Sinharay, Sanhita. Development and Application of CatalyCEST MRI Contrast Agents for the Study of Enzyme Activities in Tumor Models .

Degree: 2016, University of Arizona

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

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 October 23, 2019. 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. 23 Oct 2019.

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 2019 Oct 23]. 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

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