Date of Award


Degree Type


Degree Name

Master of Science




Dr. Luyt

Second Advisor

Dr. Kovacs

Third Advisor

Dr. John Lewis


Non-invasive imaging techniques are playing an increasingly important role in the diagnosis and treatment of cancer. The membrane protein αvβ3 integrin is selectively expressed by angiogenic blood vessels and is now established as a viable target for the molecular imaging of tumours. Previous work has demonstrated that optimal binding to αvβ3 is achieved with cyclic RGD pentapeptides. In addition, recent evidence has suggested that dimer or tetramer analogues of the cyclic RGD motif provide improved tumour uptake. RGD cyclic pentapeptides were used to target the over expression of RGD binding integrins. This was done by first imaging angiogenesis using a SPECT imaging probe and second by using a near-infrared (NIR) fluorescent probe. The SPECT image probe used a 99mTc tricarbonyl metal core, tightly bound by the tridentate chelator, histidine. 99mTc remains the most readily available and inexpensive radioisotope for medical imaging, and the tricarbonyl can be formed quickly in an aqueous mixture. The c(RGD) probe, with a 99mTc(CO)3 in a histidine chelator, was used to image tumours in a murine model. One limiting factor in the development of novel imaging agents is the throughput and quality of imaging data from the animal models currently employed for their evaluation. We have developed a number of technologies to increase the throughput of non-invasive near-infrared (NIR) imaging in an avian embryo model of human cancer by using a shell-less culture system that serves as a functional in vivo model of human cancer. The fluorescent imaging probe will consist of a cyclic RGD pentapeptide conjugated to Cy5.5, a NIR dye. In this study we demonstrate the efficacy of RGD-based iii peptide imaging probes to target αγβ3 integrin expression in human tumour cell lines. We demonstrate that imaging probe uptake can be evaluated in this system from a macroscopic (whole animal) to a microscopic level that permits the detection of single metastatic breast cancer cells. The synthesis and characterization of an imaging probe suitable for monitoring the course of type II diabetes is also presented. Glucagon-like peptide-1 (GLP-1), a 30- amino acid peptide generated by intestinal L-cells, stimulates glucose-dependent insulin secretion from beta cells of pancreatic islets. GLP-1 receptors are expressed on the surface of beta cells, making them a suitable target for in vivo imaging. We propose that the use of radiolabeled GLP-1 peptides in conjunction with SPECT could provide a method of studying islet mass throughout diabetes. A GLP-1 analogue containing the metal chelator DOTA ( 1,4,7,10-tetraazacyclododecane-1,4,7,1 O-tetraacetic acid) and naturally occurring Indium (1157113In) was prepared using solid-phase Fmoc methods. A radiolabeled 111In analogue was also prepared and used to image human islet cells.



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