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

Abstract

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(t1/2 = 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-18F]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). © 1997 John Wiley & Sons, Ltd.