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

我们能检测体内β细胞质量的变化吗？这个问题的答案由三个步骤组成：1)确定一个合适的探针，可以选择性地靶向β细胞；2)设计探针携带成像同位素或造影剂；3)选择具有适当灵敏度的成像方式来检测β细胞数量的微小变化。为了进一步了解糖尿病发病前和2型糖尿病进展过程中β细胞质量的变化，迫切需要能够检测活体动物中β细胞的成像探针。该提案将侧重于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）成像，这些探针可以结合β细胞上的GLP-1受体。这些研究的长期成果将是发现一种探针，可用于检测体内β细胞质量在糖尿病发病前、疾病过程中和再生治疗期间的变化。这具有重要的临床价值，因为它将是一个预测β细胞质量变化的工具，包括对治疗的非侵入性评估。该工具还可以检测胰岛移植，并可以跟踪胰岛功能的逐渐下降，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.