Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Medical Biophysics

Supervisor

Dr. Savita Dhanvantari

Abstract

Insulin-secreting beta cells within the Islets of Langerhans decrease in mass during the pathophysiology of diabetes. The ability to track beta cell loss in vivo by a non-invasive imaging tool would effectively identify pre-diabetes and follow islet transplant fate. The glucagon-like peptide-1 (GLP-1) receptor is expressed in the membrane of beta cells and serves as a suitable biomarker for beta cell targeting. This thesis outlines the characterization of a library of GLP-1 analogues modified to resist enzymatic degradation and carry an imaging isotope. Binding affinity, cAMP activation and plasma stability were determined to identify a candidate probe for in vitro and in vivo imaging of beta cells. Biodistribution assays revealed specific uptake of a 68Ga-GLP-1 analogue in the pancreas of C57BL/6 mice; however, beta cells were not observed in SPECT or PET images. Attempts made to reduce kidney accumulation demonstrated the need for further modifications to facilitate beta cell imaging.

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