Development of GLP-1 receptor probes for imaging changes in beta cell mass

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Can we detect changes in beta cell mass in vivo? The answer to the question is comprised of three steps: 1) identifying a suitable probe that can selectively target the beta cell; 2) engineering the probe to carry an imaging isotope or contrast agent; and 3) selecting an imaging modality that has the appropriate sensitivity to detect small changes in beta cell number. In order to advance our understanding of the changes in beta cell mass before the onset of diabetes and during the progression of Type 2 diabetes, there is a critical need for imaging probes that can detect beta cells in the living animal. This proposal will focus on the development of novel radiolabelled probes for imaging using SPECT (single photon emission computed tomography) and PET (positron emission tomography) that can bind to GLP-1 receptors on the beta cell. The long-term outcome of these studies will be the discovery of a probe that can be used to detect changes in beta cell mass in vivo before the onset of diabetes, during the course of the disease and during regenerative therapy. This is of significant clinical value as it would be a predictive tool for changes in beta cell mass including non-invasive evaluation o therapy. This tool would also permit detection of islet transplantation and could follow the progressive decline in function of the islets thereby determining when intervention is required.