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

SSR180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-Mindole-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-Mindole 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-C-11]SSR180575, where routine production batches of 4.5-5.0 GBq of radiochemically pure (>99%) i.v. injectable solutions (specific radioactivities: 50-90 GBq/mu mol) could be prepared within a total synthesis time of 25 min (HPLC purification included) starting from a 55 GBq [C-11]CO2 cyclotron production batch (non-decay-corrected overall radiochemical yields: 8-9%). The process comprises (1) trapping at 10 degrees C of [C-11]methyl triflate in DMF (300 mu l) containing 0.2-0.3 mg of the indole precursor for labeling and 4 mg of K2CO3 (excess); (2) heating at 120 degrees 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 (R) 58-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.