|作者：||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|
1CEA, I2BM, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, F‐91401 Orsay, France
2 Sanofi‐Aventis, ICMS, 1 avenue Pierre Brossolette, F‐91385 Chilly‐Mazarin, France
3 INSERM, U1023, 4 place du Général Leclerc, F‐91401 Orsay, France
4 Sanofi‐Aventis, CNS Department, 13 Quai Jules Guesde, F‐94400 Vitry‐sur‐Seine, France
5 CEA, I2BM, MIRCen, 4 place du Général Leclerc, F‐91401 Orsay, France
6 CNRS, UMR 5220; INSERM, U630; INSA de Lyon; Creatis; Bron F‐69677, France; Université de Lyon, Lyon 1, Lyon F‐69003, France.
7 Faculty of Life Sciences, AV Hill Building, University of Manchester, Manchester M13 9PT, UK.
8 CEA, Service hospitalier Frédéric Joliot, Institut d'imagerie biomédicale, 4 place du Général Leclerc, F‐91406 Orsay, France
|刊名：||Journal of Labelled Compounds and Radiopharmaceuticals, 2010, Vol.53 (13), pp.767-773|
|关键词：||carbon‐11; methylation; SSR180575; PBR; TSPO 18 kDa;|
|原始语种摘要：||Abstract(#br)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 (T1/2: 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‐ 11C]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 [11C]CO2 cyclotron production batch (non‐decay‐corrected overall radiochemical yields: 8–9%). The process comprises (1) trapping at −10°C of [11C]methyl triflate in DMF (300 µ l) containing 0.2–0.3 mg of the indole precursor for labeling and 4 mg of K2CO3 (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‐ 11C]SSR180575 as a candidate for imaging neuroinflammation with positron emission tomography are currently evaluated. Copyright © 2010 John Wiley & Sons, Ltd.|