C-labeled 2′-iododiazepam for PET studies of benzodiazepine receptors: Synthesis and comparison of biodistribution with its radioiodinated compound

For PET studies of benzodiazepine receptors, N-C-methyl-2′-iododiazepam (2′-IDZ) was synthesized by N-methylation of its desmethyl derivative withC-methyl iodide, and was subsequently purified by HPLC. The labeling and purification procedures were completed within 45 min afterC-methyl iodide trapping, and the radiochemical yield (corrected for decay) was approximately 40% based on the initial trapped radioactivity ofC-methyl iodide. Biodistribution studies in mice demonstrated thatC-2′-IDZ was rapidly and noticeably accumulated in the brain, and subsequently decreased with time. Accumulation was greater in the cortex than in other brain regions. When compared withI-2′-IDZ, the distribution was almost the same until 5 min after injection, but levels were low after 20 min. Metabolic studies indicated that the difference between these two compounds in the time course of brain radioactivity distribution may be due to N-demethylation in vivo. © 1994 Springer-Verlag.