Development of the novel diagnostic method for quantification ofpancreatic beta-cell mass by magnetic resonance imaging

在糖尿病的发生和发展过程中，胰腺β细胞的体积已知会减少。本研究的目的是建立利用磁共振成像技术测量体内β细胞体积的方法。我们首先评估了是否通过MRI的各种分析参数检测到胰岛，有或没有常见的增强剂，如gd溶液，但没有成像。其次，我们尝试使用新开发的探针进行MRI。我们将氟添加到胰高血糖素样肽-1受体（GLP-1R）的配体之一exendin（9-39）上合成探针，该配体在胰腺β细胞上特异性表达。然而，与我们的初步实验相反，根本没有检测到任何信号。用INS-1细胞系进行同样的分析也显示出类似的不良结果。这种信号差的原因被认为是由于我们的氟标记的延伸蛋白（9-39）与完整的延伸蛋白相比，对GLP-1R的亲和力极低。因此，我们在GLP-1R的另一个配体exendin-4上添加了氟，合成了新的探针，该探针与完整的exendin-4具有相似的结合亲和力。我们现在正计划用这种新探针进行核磁共振分析。

The volume of pancreatic β-cells is known to decrease during development and progression of diabetes. The aim of this study is to develop the technique of measurement of β -cell volume in vivo by using magnetic resonance imaging (MRI). We first evaluated whether pancreatic islets were detected by various analytical parameters of MRI with or without the common enhancerssuch as Gd-solution or not, however, they were not imaged. Second, we tried to perform MRI by using newly developed probe. We synthesized the probe by adding the fluorine to one of the ligands ofglucagon-like peptide-1 receptor (GLP-1R), exendin(9-39), which is specifically expressed on pancreatic β-cells. However, contrary to our preliminary experiment, no signals were detected at all. Same analysis using INS-1 cell line showed similar poor results. The reason of this poor signal was suggested to be due to the extremely low affinity of our fluorine-labeled exendin(9-39) to GLP-1R compared to intact exendins. Therefore, we synthesized new probe that fluorine was added to exendin-4, another GLP-1R ligand, and it showed similar binding affinity to intact exendins. We are now planning to perform MRI analysis by using this new probe.