Novel synthesis of [1‐¹¹C]γ‐vinyl‐γ‐aminobutyric acid ([1–¹¹C]GVG) for pharmacokinetic studies of addiction treatment

Abstract

Summaryg-Vinyl-g-aminobutyric acid (GVG, Vigabatrin 1 ), a suicide inhibitor of GABA-transaminase (GABA-T), has been suggested as a new drug for the treatment of substance abuse. In order to better understand its pharmacokinetics and potential side effects, we have developed a radiosynthesis of carbon-11 (t 1/2 =20 min) labeled GVG for positron emission tomographic (PET) studies. We report here a novel synthetic strategy to prepare the precursor and to efficiently label GVG with C-11. 5-Bromo-3-(carbobenzyloxy)amino-1-pentene was synthesized in five steps from homoserine lactone, including reduction and methylenation. This was used in a one-pot, two-step radiosynthesis. Displacement of bromide with no-carrier-added [ 11 C]cyanide followed by acid hydrolysis afforded [1-11 C]GVG with decay corrected radiochemical yields of 27 AE 9% (n=6, not optimized) with respect to [ 11 C]cyanide in a synthesis time of 45 min.

Development of a GABAergic treatment for substance abuse using PET

“…Finally, we have developed a synthetic procedure for labeling GVG with carbon-11 that is suitable for labeling both enantiomers of the drug [Zhang et al, 2002]. The availability of this tracer should allow us to study the pharmacokinetics as well as potential side effects of GVG.…”