Noninvasive islet graft imaging by PET

描述（由申请人提供）： 长期以来，人们一直希望移植的胰岛可以在活体动物中成像。这可以允许重复评估胰岛移植物质量，并提供比血糖和C肽测量更早的胰岛排斥诊断。对人类移植胰岛的非侵入性成像现在似乎是可行的，并等待从啮齿动物到非人类灵长类动物，然后到人类的翻译。 我们将测试以下假设：1）报告基因的病毒递送，随后进行光学和microPET成像，提供了门静脉内胰岛移植后无创监测胰岛细胞质量的新模式; 2）光学和microPET成像可以比血糖和C肽水平的测量更早地检测胰岛排斥反应。此外，我们将评估病毒感染和长期PET报告基因表达是否对胰岛移植物有害。最后，作为向非人灵长类动物扩展胰岛移植物成像的一步，我们将鉴定有效地抑制非人灵长类动物胰岛的rAAV载体，并研究长期成像报告基因表达对非人灵长类动物胰岛功能的影响。总之，这项建议的结果将提供一个显着的进步，翻译胰岛成像从一个有前途的实验室观察到一个临床现实。

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.