Automated radiosynthesis of GMP quality [18 F]HX4 for PET imaging of hypoxia

Abstract Introduction [18 F]HX4 is a 2-nitroimidazole based investigational radiotracer for imaging hypoxia. Methods A two-step, one-pot synthetic procedure was developed on a GE Tracerlab MX-FDG with a disposable cassette. Nucleophilic substitution of a nosylate group with [18 F]fluoride was followed by solvent evaporation and acidic removal of the acetyl protecting group. HPLC purification in a bio-compatible solvent mixture was developed. Results and conclusions Using starting activities of 80–110 GBq [18 F]fluoride, GMP compliant [18 F]HX4 was produced in non-decay corrected radiochemical yields of 12 ± 3% (n = 9) in 55 min including HPLC purification. No reformulation steps were required. The mean specific activity of the final product was 2450 GBq/μmol. Modifications to the process and final formulation were included to prevent decomposition of the product, and these changes resulted in an improved stability of the formulated [18 F]HX4, with a shelf-life of at least 8 h post-synthesis. The product consistently passed all required quality control tests to determine that the [18 F]HX4 was suitable for clinical use. Using a 90 minute target bombardment, and 80–110 GBq starting [18 F]fluoride, the method produced multiple patient doses.