Automated radiosynthesis of no-carrier-added [S-fluoromethyl-18F] fluticasone propionate as a radiotracer for lung deposition studies with PET

Article abstract of DOI:10.1002/(SICI)1099-1344(199707)39:7<567::AID-JLCR999>3.0.CO;2-P

Fluticasone propionate [(S)-fluoromethyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α -(propionyloxy)-androsta-1,4-diene-17β-carbothioate; FP] is a potent anti-inflammatory steroid with several therapeutic indications, including use as an anti-asthmatic drug when administered as sized particles by inhalation from a pressurised metered-dose inhaler (pMDI). FP was successfully labelled with fluorine-18 (t( 1/4 ) = 109.6 min: β+ = 100%) by displacement of tosylate with cyclotron-produced no-carrier-added [¹⁸F]fluoride in an (S)-tosylmethyl precursor prepared from the known (S)-chloromethyl analogue of FP. Radiochemically pure [S-/fluoromethyl-¹⁸]FP was separated by reverse phase HPLC in 35% radiochemical yield (decay-corrected) within 80 min from the end of radionuclide production (as verified by, radio-HPLC, LC-MS and LC-NMR). The radiosynthesis was automated for the safe production of high radioactivities (20-50 mCi) of [¹⁸F]FP in a lead-shielded hot-cell for subsequent incorporation into formulated FP particles within a pMDI and subsequent study of FP deposition in human lung using positron emission tomography (PET).