Date of Award

Spring 5-9-2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Jenny J. Yang

Second Advisor

Robert Wohlhueter

Third Advisor

Siming Wang

Fourth Advisor

Ming Luo

Abstract

MRI is a noninvasive technique used for disease diagnosis. However, recent clinically used MRI contrast agents exhibit low relaxivity, high metal toxicity due to low dose efficiency and inability to target specific diseased cells. To address the pressing unmet clinical needs, we developed a novel class of protein-based contrast agent, with improved sensitivity, high relaxivity with better metal selectivity, stability and low toxicity. A GRPR-targeted ProCA1 variants designed to selectively target prostate cancer via molecular imaging, were successfully expressed in bacterial expression system and tagless purification, showed about 12 fold higher relaxivities as compared to Gd-DTPA.hProCA32demonstrated strong Gd3+ binding affinity with Kd of 10-22 M and strong selectivity forGd3+ overCa2+and Zn2+, high r1 (28 mM-1 s -1) and r2 (35 mM -1 s -1) and PEGylated-hProCA32 showed excellent in vitro serum stability for 12 days. These studies demonstrate stronger translational potentials of ProCAs for human applications.

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