Synthesis of 18F-labeled streptozotocin derivatives and an in-vivo kinetics study using positron emission tomography |
| |
| Affiliation: | 1. Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607–8414, Japan;2. Department of Systems and Informatics, Hokkaido Information University, 59-2 Nishi-Nopporo, Ebetsu, Hokkaido 069-8585, Japan;3. Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikada-cho, Kita-ku, Okayama 700-8558, Japan;4. Department of Nuclear Medicine and Comprehensive Heart Failure Centre (CHFC), Julius-Maximilian-University of Würzburg, Oberderrbacherstr. 6, 97080 Würzburg, Germany;1. Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, No. 19 Xinjiekouwai Street, Haidian District, Beijing 100875, China;2. College of Chemistry and Chemical Engineering, Anyang Normal University, No. 436 Xian''ge Road, Anyang 455000, Henan Province, China;1. Instituto de Química del Sur (INQUISUR), Departamento de Química, Universidad Nacional del Sur (UNS)-CONICET, Av. Alem 1253, B8000CPB, Bahía Blanca, Argentina;2. CERZOS UNS-CONICET CCT-Bahía Blanca, Camino La Carrindanga Km7, B8000FWB, Bahía Blanca, Argentina;3. Departamento de Biología Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000CPB, Bahía Blanca, Argentina;1. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, 9, Lavrent’ev ave., Novosibirsk 630090, Russian Federation;2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, 8, Lavrent’ev ave., Novosibirsk 630090, Russian Federation;3. Novosibirsk State University, 2, Pirogova Str., Novosibirsk 630090, Russian Federation;1. Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China;2. The College of Life Sciences, State Key Laboratory of Virology, Modern Virology Research Center, Wuhan University, Wuhan 430072, China;3. Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China |
| |
| Abstract: | Glucose transporter 2 (GLUT2) is involved in glucose uptake by hepatocytes, pancreatic beta cells, and absorptive 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 introduced 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. |
| |
| Keywords: | Streptozotocin Glucose transporter 2 Fluorine-18 labeling Positron emission tomography Type-2 diabetes Metabolic syndrome |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
