Novel synthesis of (11C)GVG (Vigabatgrin) for pharmacokinetic studies ofaddiction treatment

摘要

We report here a novel synthetic route to prepare the precursor and toefficiently label GVG with C-11. 5-Bromo-3-(carbobenzyloxy) amino-1-pentene was synthesized in five steps from homoserine lactone. This was used in a two step radiosynthesis, displacement with ((sup 11)C)cyanide followed by acid hydrolysis to afford ((sup 11)C)GVG with high radiochemical yields (> 35%, not optimized) and high specific activity (2-5 Ci/(micro)mol). The ((sup 11)C)cyanide trapping was achieved at (minus)5 C with a mixture of Kryptofix and K(sub 2)CO(sub 3) without using conventional aqueous trapping procedure (7). At this temperature, the excess NH(sub 3) from the target that may interfere with the synthesis would not be trapped (8). This procedure would be advantageous to any moisture sensitive radiosynthetic steps, as it was the case for our displacement reaction. When conventional aqueous trapping procedure was used, any trace amount of water left, even after prolonged heating, resulted in either no reaction or extremely low yields for the displacement reaction. The entire synthetic procedure should