Synthesis of [18F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist's perspective

Torsten Kniess; Jörg Zessin; Peter Mäding; Manuela Kuchar; Oliver Kiss; Klaus Kopka

doi:10.1186/s41181-023-00190-7

Synthesis of [¹⁸F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist's perspective

EJNMMI Radiopharm Chem. 2023 Mar 10;8(1):5. doi: 10.1186/s41181-023-00190-7.

Authors

Torsten Kniess¹, Jörg Zessin², Peter Mäding², Manuela Kuchar², Oliver Kiss², Klaus Kopka^{2

3

4

5}

Affiliations

¹ Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany. t.kniess@hzdr.de.
² Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.
³ Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, Mommsenstraße 4, 01069, Dresden, Germany.
⁴ National Center for Tumor Diseases (NCT) Dresden, University Hospital Carl Gustav Carus, Fetscherstraße 74, 01307, Dresden, Germany.
⁵ German Cancer Consortium (DKTK), Partner Site Dresden, Fetscherstraße 74, 01307, Dresden, Germany.

Abstract

Background: [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO, 1H-1-(3-[¹⁸F]fluoro-2-hydroxypropyl)-2-nitroimidazole) is a commonly used radiotracer for imaging hypoxic conditions in cells. Since hypoxia is prevalent in solid tumors, [¹⁸F]FMISO is in clinical application for decades to explore oxygen demand in cancer cells and the resulting impact on radiotherapy and chemotherapy.

Results: Since the introduction of [¹⁸F]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 [¹⁸F]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.

Conclusion: In a GMP compliant radiosynthesis using original cassettes for FASTlab we produced [¹⁸F]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 [¹⁸F]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.

Keywords: Automated radiosynthesis; FASTlab; [18F]FMISO; [18F]fluoromisonidazole.