Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan..
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Nucl Med Biol. 2020 Nov-Dec;90-91:93-97. doi: 10.1016/j.nucmedbio.2020.10.003. Epub 2020 Oct 26.
The deposition of islet amyloid composed of amylin aggregates is related to β-cell mass dysfunction in type 2 diabetes mellitus (T2DM), and it may be involved in the development and progression of T2DM. In this study, we newly designed, synthesized, and evaluated a radiogallium-labeled pyridyl benzofuran derivative ([Ga]GPBF) as an amylin imaging probe.
An in vitro competitive inhibition assay was performed to determine the binding affinity for amylin aggregates. An in vitro autoradiographic study was carried out using pancreatic sections from a T2DM patient. A biodistribution of [Ga]GPBF in normal mice was evaluated. Finally, we carried out ex vivo autoradiography using mouse transplanted with amylin aggregates.
GPBF exhibited binding affinity for amylin aggregates in vitro. In addition, [Ga]GPBF clearly labeled islet amyloids in in vitro autoradiography of a T2DM pancreatic section. In a biodistribution study using normal mice, [Ga]GPBF showed initial uptake into the pancreas, but non-specific accumulation in the liver, spleen, and pancreas was also observed. Furthermore, an ex vivo autoradiogram demonstrated that [Ga]GPBF bound to amylin aggregates in the pancreas of the amylin aggregate-transplanted mice.
These results provide useful insights into the development of radiogallium labeled probes that target amylin aggregates in the T2DM pancreas.
由胰岛淀粉样蛋白组成的沉积物与 2 型糖尿病（T2DM）中的β细胞质量功能障碍有关，它可能参与了 T2DM 的发生和发展。在本研究中，我们新设计、合成并评估了一种放射性镓标记的吡啶苯并呋喃衍生物（[Ga]GPBF）作为淀粉样蛋白成像探针。
进行体外竞争性抑制试验以确定对胰岛淀粉样蛋白聚集体的结合亲和力。使用 T2DM 患者的胰腺切片进行体外放射自显影研究。评估 [Ga]GPBF 在正常小鼠中的生物分布。最后，我们使用移植有淀粉样蛋白聚集体的小鼠进行了离体放射自显影。
GPBF 在体外显示出对胰岛淀粉样蛋白聚集体的结合亲和力。此外，[Ga]GPBF 清楚地标记了 T2DM 胰腺切片体外放射自显影中的胰岛淀粉样蛋白。在使用正常小鼠的生物分布研究中，[Ga]GPBF 最初被胰腺摄取，但也观察到肝脏、脾脏和胰腺的非特异性积聚。此外，离体放射自显影显示 [Ga]GPBF 与移植有淀粉样蛋白聚集体的小鼠胰腺中的淀粉样蛋白聚集体结合。
这些结果为开发针对 T2DM 胰腺中淀粉样蛋白聚集体的放射性镓标记探针提供了有用的见解。
