Synthesis of 18F-labeled streptozotocin derivatives and an in-vivo kinetics study using positron emission tomography
Synthesis of 18F-labeled streptozotocin derivatives and an in-vivo kinetics study using positron emission tomography
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DOI：
10.1016/j.bmcl.2020.127400
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发表时间：
2020-09-01
影响因子：
2.7
通讯作者：
Kimura, Hiroyuki
中科院分区：
文献类型：
--
作者：
Arimitsu, Kenji;Yagi, Yusuke;Kimura, Hiroyuki
葡萄糖转运蛋白2（GLUT 2）参与肝细胞、胰腺β细胞和肠吸收细胞以及肾脏近端小管的葡萄糖摄取。胰腺GLUT 2在葡萄糖刺激的胰岛素分泌机制中也起重要作用。在这项研究中，新的氟-18-标记的链脲佐菌素（STZ）衍生物的合成，作为糖苷类似物在体内GLUT 2成像。在化合物的3 ′-位引入氟原子，使其成为己基，目的是合成比STZ更稳定的化合物。亚硝基衍生物在放射合成后的纯化和纯度分析过程中表现出相对较好的稳定性。然后，我们在PET成像和离体生物分布研究中评估了化合物。我们在肝脏和肾脏中观察到高水平的放射性，这表明在给药后5分钟内在这些器官中蓄积。相反，脱亚硝基衍生物仅在给药后不久在肾脏和膀胱中蓄积。因此，预期具有亚硝基的化合物会在GLUT 2表达器官中蓄积，亚硝基的存在对于体内GLUT 2成像至关重要。
Glucose transporter 2 (GLUT2) is involved in glucose uptake by hepatocytes, pancreatic beta cells, and ab-sorptive cells in the intestine and proximal tubules in the kidney. Pancreatic GLUT2 also plays an important role in the mechanism of glucose-stimulated insulin secretion. In this study, novel Fluorine-18-labeled streptozotocin (STZ) derivatives were synthesized to serve as glycoside analogs for in-vivo GLUT2 imaging. Fluorine was in-troduced to hexyl groups at the 3'-positions of the compounds, and we aimed to synthesize compounds that were more stable than STZ. The nitroso derivatives exhibited relatively good stability during purification and purity analysis after radiosynthesis. We then evaluated the compounds in PET imaging and ex-vivo biodistribution studies. We observed high levels of radioactivity in the liver and kidney, which indicated accumulation in these organs within 5 min of administration. In contrast, the denitroso derivatives accumulated only in the kidney and bladder shortly after administration. Compounds with nitroso groups are thus expected to accumulate in GLUT2-expressing organs, and the presence of a nitroso group is essential for in-vivo GLUT2 imaging.