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 (T1/2: 20.38 min) in one chemical step using the following process: (i) reaction of [11C]phosgene with the corresponding ring-opened precursor (1.2–2.5 mg) at 100°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® C18. A total of 300–500 MBq of [11C]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/µmol (3.5–7% decay-corrected radiochemical yield, based on starting [11C]CH4). Copyright © 2008 John Wiley & Sons, Ltd.

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