Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Chemistry

Supervisor

Dr. Leonard G. Luyt

Abstract

Contemporary diagnostic techniques for prostate cancer (PCa) have a limited ability to distinguish between benign and malignant disease. The ghrelin receptor has a differential expression in normal, benign and cancerous prostatic tissue. Targeting this receptor with 18F-radiolabelled peptidomimetics would enable differentiation between these disease states via PET imaging. A series of 19F-peptidomimetics were synthesized and characterized by HRMS, HPLC and 1 H-NMR spectroscopy in order to test locations for 18F radioisotope insertion. Competitive receptor binding assays using HEK293/GHS-R1a cells were used to evaluate compound binding affinities. This led to the identification of two lead compounds: [1-Nal4,Lys5(4-FB)]G-7039 (IC50 = 69 nM) and [Lys5(2-FP)]G-7039 (IC 50 = 19 nM). Prosthetic group radiolabelling of [1-Nal4,Lys5(4-FB)]G-7039 using N-succinimidyl 4-[18 F]fluorobenzoate gave radiochemical yields of 51-52%, radio-purity > 98% and specific activity of 116 MBq/μmol after 127 minutes at end-of-synthesis. Successful 18F-radiolabelling of [1-Nal4, Lys5(4-FB)]G-7039 highlights its potential for use as a PET imaging agent for early-stage PCa diagnosis.


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