Radiosynthesis of (S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)benzo[d]isoxazol-3-yl]oxazolidin-2-[11C]one ([11C]SL25.1188), a novel radioligand for imaging monoamine oxidase-B with PET

Within a novel series of 2-oxazolidinones developed in the past by Sanofi-Synthelabo, SL25.1188 ((S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)benzo[d]isoxazol-3-yl]oxazolidin-2-one), a compound that inhibits selectively and competitively MAO-B in human and rat brain (Ki values of 2.9 and 8.5 nM for MAO-B, respectively, and ED50 ((rat)): 0.6 mg/kg p.o.), was considered an appropriate candidate for imaging this enzyme with positron emission tomography. SL25.1188 was labelled with carbon-11 (T-1/2: 20.38 min) in one chemical step using the following process: (i) reaction of [C-11]phosgene with the corresponding ring-opened precursor (1.2-2.5 mg) at 100 degrees C for 2 min in dichloromethane (0.5 mL) followed by (ii) concentration to dryness of the reaction mixture and finally (iii) semi-preparative HPLC purification on a Waters Symmetry (R) C18. A total of 300-500 MBq of [C-11]SL25.1188 (>95% chemically and radiochemically pure) could be obtained within 30-32 min (Sep-pak-based formulation included) with specific radioactivities ranging from 50 to 70 GBq/mu mol (3.5-7% decay-corrected radiochemical yield, based on starting [C-11]CH4).