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

我们能检测体内β细胞群的变化吗？这个问题的答案由三个步骤组成：1）识别可以选择性靶向β细胞的合适探针; 2）设计探针以携带成像同位素或造影剂;以及3）选择具有适当灵敏度的成像模式以检测β细胞数量的微小变化。为了促进我们对糖尿病发病前和2型糖尿病进展期间β细胞质量变化的理解，迫切需要能够检测活体动物中β细胞的成像探针。该提案将重点开发新型放射性标记探针，用于使用SPECT（单光子发射计算机断层扫描）和PET（正电子发射断层扫描）进行成像，可与β细胞上的GLP-1受体结合。这些研究的长期结果将是发现一种探针，可用于检测糖尿病发作前、疾病过程中和再生治疗期间体内β细胞群的变化。这具有重要的临床价值，因为它将是β细胞质量变化的预测工具，包括治疗的非侵入性评价。该工具还将允许检测胰岛移植，并且可以跟踪胰岛功能的进行性下降，从而确定何时需要干预。

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.