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


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 8h 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.
PETNET Solutions, Heathfield Way, Nottingham City Hospital, Gate 1 Hucknall Road, Nottingham, NG5 1PB, UK.
David R
DR
Turton
Nottingham University Hospitals NHS Trust, PET/CT Centre, Nottingham City Hospital, Gate 1 Hucknall Road, Nottingham, NG5 1PB, UK. Electronic address: helen.betts@nottingham.ac.uk.
Helen M
HM
Betts
PETNET Solutions, Heathfield Way, Nottingham City Hospital, Gate 1 Hucknall Road, Nottingham, NG5 1PB, UK.
David
D
Dutton
Nottingham University Hospitals NHS Trust, PET/CT Centre, Nottingham City Hospital, Gate 1 Hucknall Road, Nottingham, NG5 1PB, UK; University of Nottingham, School of Medicine, Queen's Medical Centre, Derby Road, Nottingham, NG7 2UH, UK.
Alan C
AC
Perkins
D001331:Automation; D000860:Hypoxia / Q000000981:diagnostic imaging*; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D011786:Quality Control; D011854:Radiochemistry / Q000379:methods*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
C553729:3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol; D009593:Nitroimidazoles; D014230:Triazoles
Fluorine-18; GMP; HX4; Hypoxia; Radiostabiliser; Radiosynthesis