Automated synthesis of the ultra high specific activity of [11C]Ro15-4513 and its application in an extremely low concentration region to an ARG study

We have designed and constructed an automated device for the production of ultra-high specific activity C-11-labeled compounds via [C-11]CH3I synthesized by the single pass I-2 method. The optimum condition for the production of [C-11]CH3I was determined to be 630degreesC for oven-1 (reaction column), 50degreesC for oven-2 (iodine column) and 50 ml/rain for the He gas flow rate, and gave the maximum conversion ratio of [C-11]CH3I. 44%. [C-11]RoI5-4513, known as an inverse agonist of the benzodiazepine receptor, was produced under optimized conditions. An i.v. injectable [C-11]Ro15-4513 solution of 1500 +/- 490 MBq (n = 6) with specific activity 4700 +/- 2500 GBq/mumol and a radiochemical Purity of 98.2 +/- 2% was obtained automatically within 25 minutes (from EOB) by irradiating nitrogen gas containing 5% H-2 with 18 Mev protons (14.2 MeV on target) at 20 muA for 20 minutes. The highest specific activity of 9700 GBq/mumol (at EOS) could be achieved, although the radiochemical purity was 92.4%. By the use of the ultra-hi h specific activity [C-11]Ro15-4513, the super high 9 affinity binding, sites in the rat brain hippocampus could be clearly visualized even at the extremely low concentration of 0.66pM Ro15-4513 by invitro autoradiography. (C) 2003 Elsevier Science Inc. All rights reserved.