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-b]indole-1-acetamide) is the lead compound of an original pyridazino-indole 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-methyl-pyridazino[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 (499%) 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 [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 μl) 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 (ZorbaxR SB-C-18). In vivo pharmacological properties of [indole-N-methyl-11C]SSR180575 as a candidate for imaging neuro-inflammation with positron emission tomography are currently evaluated. (authors)