Radiosynthesis of 7-chloro-N,N-dimethyl-5-[11C]methyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, [11C]SSR180575, a novel radioligand for imaging the TSPO (peripheral benzodiazepine receptor) with PET

✍ Scribed by Cyrille Thominiaux; Annelaure Damont; Bertrand Kuhnast; Stéphane Demphel; Stéphane Le Helleix; Sabine Boisnard; Luc Rivron; Fabien Chauveau; Hervé Boutin; Nadia Van Camp; Raphaël Boisgard; Sébastien Roy; John Allen; Thomas Rooney; Jesus Benavides; Philippe Hantraye; Bertrand Tavitian; Frédéric Dollé

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: French
• Weight: 168 KB
• Volume: 53
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1794

✦ Synopsis

Abstract

SSR180575 (7‐chloro‐N,__N,5‐trimethyl‐4‐oxo‐3‐phenyl‐3,5‐dihydro‐4__H‐pyridazino[4,5‐b]indole‐1‐acetamide) is the lead compound of an original pyridazinoindole series of potent and highly selective TSPO (peripheral benzodiazepine receptor) ligands. Isotopic labeling of SSR180575 with the short‐lived positron‐emitter carbon‐11 (T~1/2~: 20.38 min) at its 5‐methylpyridazino[4,5‐b]indole moiety as well as at its N,N‐dimethylacetamide function by methylation of the corresponding nor‐analogues was investigated. Best results in terms of radiochemical yields and purities were obtained for the preparation of [indole‐N‐methyl‐^11^C]SSR180575, where routine production batches of 4.5–5.0 GBq of radiochemically pure (>99%) i.v. injectable solutions (specific radioactivities: 50–90 GBq/µmol) could be prepared within a total synthesis time of 25 min (HPLC purification included) starting from a 55 GBq [^11^C]CO~2~ cyclotron production batch (non‐decay‐corrected overall radiochemical yields: 8–9%). The process comprises (1) trapping at −10°C of [^11^C]methyl triflate in DMF (300 µl) containing 0.2–0.3 mg of the indole precursor for labeling and 4 mg of K~2~CO~3~ (excess); (2) heating at 120°C for 3 min; (3) dilution of the residue with 0.5 ml of the HPLC mobile phase and (4) purification using semi‐preparative reversed‐phase HPLC (Zorbax^®^ SB‐C‐18). In vivo pharmacological properties of [indole‐N‐methyl‐^11^C]SSR180575 as a candidate for imaging neuroinflammation with positron emission tomography are currently evaluated. Copyright © 2010 John Wiley & Sons, Ltd.