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

✍ Scribed by Yann Bramoullé; Frédéric Puech; Wadad Saba; Heric Valette; Michel Bottlaender; Pascal George; Frédéric Dollé

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 156 KB
• Volume: 51
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1492

✦ Synopsis

Abstract

Within a novel series of 2‐oxazolidinones developed in the past by Sanofi‐Synthélabo, 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 ED~50 (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 [^11^C]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 [^11^C]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 [^11^C]CH~4~). Copyright © 2008 John Wiley & Sons, Ltd.