Kniess Torsten, Zessin Jörg, Mäding Peter, Kuchar Manuela, Kiss Oliver, Kopka Klaus
Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.
Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, Mommsenstraße 4, 01069, Dresden, Germany.
EJNMMI Radiopharm Chem. 2023 Mar 10;8(1):5. doi: 10.1186/s41181-023-00190-7.
[F]fluoromisonidazole ([F]FMISO, 1H-1-(3-[F]fluoro-2-hydroxypropyl)-2-nitroimidazole) is a commonly used radiotracer for imaging hypoxic conditions in cells. Since hypoxia is prevalent in solid tumors, [F]FMISO is in clinical application for decades to explore oxygen demand in cancer cells and the resulting impact on radiotherapy and chemotherapy.
Since the introduction of [F]FMISO as positron emission tomography imaging agent in 1986, a variety of radiosynthesis procedures for the production of this hypoxia tracer has been developed. This paper gives a brief overview on [F]FMISO radiosyntheses published so far from its introduction until now. From a radiopharmaceutical chemist's perspective, different precursors, radiolabeling approaches and purification methods are discussed as well as used automated radiosynthesizers, including cassette-based and microfluidic systems.
In a GMP compliant radiosynthesis using original cassettes for FASTlab we produced [F]FMISO in 49% radiochemical yield within 48 min with radiochemical purities > 99% and molar activities > 500 GBq/µmol. In addition, we report an easy and efficient radiosynthesis of [F]FMISO, based on in-house prepared FASTlab cassettes, providing the radiotracer for research and preclinical purposes in good radiochemical yields (39%), high radiochemical purities (> 99%) and high molar activity (> 500 GBq/µmol) in a well-priced option.
[F]氟米索硝唑（[F]FMISO，1H-1-(3-[F]氟-2-羟丙基)-2-硝基咪唑）是一种常用的放射性示踪剂，用于细胞缺氧状态成像。由于缺氧在实体瘤中普遍存在，[F]FMISO已临床应用数十年，以探索癌细胞中的氧需求及其对放疗和化疗的影响。
自1986年[F]FMISO作为正电子发射断层扫描成像剂引入以来，已开发出多种用于生产这种缺氧示踪剂的放射性合成方法。本文简要概述了从引入[F]FMISO至今已发表的放射性合成方法。从放射性药物化学家的角度，讨论了不同的前体、放射性标记方法和纯化方法，以及所使用的自动化放射性合成仪，包括基于盒式和微流控系统。
在使用FASTlab原装盒的符合GMP标准的放射性合成中，我们在48分钟内以49%的放射化学产率制备了[F]FMISO，放射化学纯度>99%，摩尔活度>500GBq/µmol。此外，我们报告了一种基于内部制备的FASTlab盒的简便高效的[F]FMISO放射性合成方法，以合理的价格提供用于研究和临床前目的的放射性示踪剂，放射化学产率良好（39%），放射化学纯度高（>99%），摩尔活度高（>500GBq/µmol）。
