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

Abstract

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 (&gt;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 &amp; Sons, Ltd.