Noninvasive islet graft imaging by PET

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DESCRIPTION (provided by applicant): It has been longed hoped that transplanted islets could be imaged in living animals. This could allow the repeated assessment islet graft mass and provide an earlier diagnosis of islet rejection than measurements of blood glucose and C-peptide. The noninvasive imaging of transplanted islets in man now appears to be feasible, and awaits translation from rodents to nonhuman primates, and then to humans. We will test the hypotheses that; 1) the viral delivery of reporter genes, followed by optical and microPET imaging, provide new modalities to noninvasively monitor islet cell mass after intraportal islet transplantation and 2) optical and microPET imaging can detect islet rejection earlier than measurements of blood glucose and C-peptide levels. Furthermore, we will evaluate whether viral infection and long-term PET reporter expression is deleterious to the islet graft. Finally, as a step toward extending islet graft imaging to nonhuman primates, we will identify rAAV vectors that efficiently transduce nonhuman primate islets, and examine the effect of long-term imaging reporter gene expression on nonhuman primate islet function. Together, the results of this proposal will provide a significant advance towards translating islet imaging from a promising bench observation to one of clinical reality.