AUTOMATED RADIOSYNTHESIS OF NO-CARRIER-ADDED [S-FLUOROMETHYL-F-18]FLUTICASONE PROPIONATE AS A RADIOTRACER FOR LUNG DEPOSITION STUDIES WITH PET

Fluticasone propionate [(S)-fluoromethyl-6 alpha,9 alpha-difluoro-11 b eta-hydroxy-16 alpha-methyl-3-oxo-17 alpha-(propionyloxy)-androsta-1,4 -diene-17 beta-carbothioate; FP] is a potent anti-inflammatory steroid with several therapeutic indications, including use as an anti-asthma tic drug when administered as sized particles by inhalation from a pre ssurised metered-dose inhaler (pMDI). FP was successfully labelled wit h fluorine-18 (t(1/2) = 109.6 min; beta(+) = 100%) by displacement of tosylate with cyclotron-produced no-carrier-added [F-18]fluoride in an (S)-tosylmethyl precursor prepared from the known (S)-chloromethyl an alogue of FP. Radiochemically pure [S-fluoromethyl-F-18]FP was separat ed by reverse phase HPLC in 35% radiochemical yield (decay-corrected) within 80 min form the end of radionuclide production (as verified by, radio-HPLC, LC-MS and LC-NMR). The radiosynthesis was automated for t he safe production of high radioactivities (20-50 mCi) of [F-18]FP in a lead-shielded hot-cell for subsequent incorporation into formulated FP particles within a pMDI and subsequent study of FP deposition in hu man lung using positron emission tomography (PET).