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

Abstract

We have designed and constructed an automated device for the production of ultra-high specific activity 11C-labeled compounds via [ 11C]CH 3I synthesized by the single pass I 2 method. The optimum condition for the production of [ 11C]CH 3I was determined to be 630°C for oven-1 (reaction column), 50°C for oven-2 (iodine column) and 50 ml/min for the He gas flow rate, and gave the maximum conversion ratio of [ 11C]CH 3I, 44%. [ 11C]Ro15-4513, known as an inverse agonist of the benzodiazepine receptor, was produced under optimized conditions. An i.v. injectable [ 11C]Ro15-4513 solution of 1500 ± 490 MBq (n = 6) with specific activity 4700 ± 2500 GBq/μmol 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 μA for 20 minutes. The highest specific activity of 9700 GBq/μmol (at EOS) could be achieved, although the radiochemical purity was 92.4%. By the use of the ultra-high specific activity [ 11C]Ro15-4513, the super high affinity binding sites in the rat brain hippocampus could be clearly visualized even at the extremely low concentration of 0.66 pM Ro15-4513 by in vitro autoradiography.