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

• Published in: Journal of labelled compounds & radiopharmaceuticals 2010-11, Vol.53 (13), p.767-773
• Main Authors: Thominiaux, Cyrille, Damont, Annelaure, Kuhnast, Bertrand, Demphel, Stéphane, Le Helleix, Stéphane, Boisnard, Sabine, Rivron, Luc, Chauveau, Fabien, Boutin, Hervé, Van Camp, Nadia, Boisgard, Raphaël, Roy, Sébastien, Allen, John, Rooney, Thomas, Benavides, Jesus, Hantraye, Philippe, Tavitian, Bertrand, Dollé, Frédéric
• Format: Article
• Language: English
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.1794

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/ µ mol) 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  µ l) 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.