Automated synthesis of hypoxia imaging agent [¹⁸F]FMISO based upon a modified Explora FDG₄ module

Abstract

A new automated synthesis procedure of 1-H-1-(3-[¹⁸F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([¹⁸F]FMISO), a specific hypoxia imaging agent with great significances for the noninvasive, dynamic hypoxia evaluation of cancer, was developed by modifying Explora FDG₄ module, a commercial [¹⁸F]FDG production system, in this study. Its radiochemical synthesis was carried out via two sequent reaction steps, i.e. the nucleophilic displacement of labeling precursor 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-tosyl-propanediol (NITTP) with activated ¹⁸F- ion at 100 °C for 8 minutes, and the following hydrolysis with 1M HCl at 100 °C for 5 minutes and neutralization with 1M NaOH. Two-pot reaction with two independent separations was adopted to assure the good separation of final product via solid phase extraction (SPE) based upon combined Sep-pak cartridges instead of high performance liquid chromatography (HPLC). This fast, reliable preparation route of ¹⁸F-FMISO could complete within 50 minutes with about 55% of high radiochemical yield (with decay correction) and more than 98% of good radiochemical purity. The modified module could perform multiple runs of production of [¹⁸F]FMISO.