Synthesis of [F]FMISO, a Hypoxia-specific Imaging Probe for PET, an Overview from a Radiochemist's Perspective

Overview

Journal EJNMMI Radiopharm Chem

Date 2023 Mar 10

PMID 36897480

Authors

Torsten Kniess

Jorg Zessin

Peter Mading

Manuela Kuchar

Oliver Kiss

Klaus Kopka

Affiliations

Soon will be listed here.

Abstract

Background: [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.

Results: 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.

Conclusion: 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.

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