Date of Award
Master of Science
Dr. Savita Dhanvantari
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.
Rota, Vanessa Amanda, "CHARACTERIZING NOVEL GLUCAGON-LIKE PEPTIDE-1 DERIVATIVES FOR NUCLEAR IMAGING OF THE PANCREATIC BETA CELLS" (2011). Digitized Theses. 3321.