Non-Invasive Imaging of Beta Cell Mass
Pancreatic islet transplantation is a minimally invasive procedure that can restore normoglycemia and insulin independence in T1D without the surgical complications associated with vascularized whole pancreas transplantation. The long-term outcomes of islet cell transplantation, however, have remained suboptimal due to islet loss. There is an urgent need to develop a methodology to monitor in vivo islet mass and function, which would greatly assist efforts to improve long-term islet transplantation outcomes. However, due to the lack of available tools to monitor islets post-transplant, estimates of their survival and function are limited to indirect assessments. Such assessments, which are based on changes in patient insulin requirements or metabolism, may be influenced and rendered inaccurate by fluctuations in the metabolic state and insulin secretory capacity of beta cells under various physiologic and pathophysiologic conditions. The goal of this research is to develop a non-invasive methodology for quantitatively monitoring transplanted islets. Specifically, positron emission tomography (PET) probes with high specific activity will be developed for noninvasive in vivo islet imaging. Our current experimental results indicate that [68Ga]DO3A-VS-Cys40-Exendin-4 is a promising PET candidate for imaging beta cells with high resolution in vivo. We have already completed most of the elements required for an IND application and the synthesis of a new batch of clinical grade precursor compound is currently ongoing. We are very thankful for the support of the Larry L. Hillblom Foundation in our efforts to bring this new imaging technology to the clinic.