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

Abstract

Introduction[18F]HX4 is a 2-nitroimidazole based investigational radiotracer for imaging hypoxia. MethodsA 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 [18F]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 conclusionsUsing starting activities of 80–110GBq [18F]fluoride, GMP compliant [18F]HX4 was produced in non-decay corrected radiochemical yields of 12±3% (n=9) in 55min including HPLC purification. No reformulation steps were required. The mean specific activity of the final product was 2450GBq/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 [18F]HX4, with a shelf-life of at least 8h post-synthesis. The product consistently passed all required quality control tests to determine that the [18F]HX4 was suitable for clinical use. Using a 90minute target bombardment, and 80–110GBq starting [18F]fluoride, the method produced multiple patient doses.