SYNTHESIS AND PET IMAGING OF THE BENZODIAZEPINE RECEPTOR TRACER [N-METHYL-C-11]IOMAZENIL

The central benzodiazepine receptor tracer [N-methyl-C-11]iomazenil (Ro 16-0154) was synthesized by alkylation of the desmethyl precursor noriomazenil with [C-11]methyl iodide. The [C-11]CH3I (prepared by reduction of [C-11]CO2 with LiAlH4 followed by reaction with HI) was reacted with noriomazenil in N,N-dimethylformamide and Bu(4)N(+)OH(-) for 1 min at 80 degrees C and purified by HPLC (C-18, 34% CH3CN/H2O, 7 mL/min). The product was obtained with synthesis time 35 +/- 5 min (mean +/- SD, n = 7), radiochemical yield (EOB) 36 +/- 16%, radiochemical purity 99 +/- 1%, and specific activity 5100 +/- 2800 mCi/mu mol. Absorbed radiation doses were calculated from previously acquired human biodistribution data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8 h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After i.v. injection of [C-11]iomazenil in an adult baboon or healthy human volunteer, radioactivity accumulated in the cortex with time-activity curves in agreement with results obtained with [C-11]flumazenil PET and [I-123]iomazenil SPECT studies. The count rate was sufficient to obtain quantitative images up to 2 h post-injection with a 14 mCi injection. These results suggest that [C-11]iomazenil will be a useful agent for measuring benzodiazepine receptors in vivo by positron emission tomography.