N-[C-11]methyl-3,4-methylenedioxyamphetamine (Ecstasy) and 2-methyl-N-[C-11]methyl-4,5-methylenedioxyamphetamine: Synthesis and biodistribution studies

In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA), 2 and 2,N-dimethyl- 4,5-methylenedioxyamphetamine (MADAM-6) 4 were prepared for application in in-vivo PET studies by methylation of 3,4-metbylenedioxyamphetamine (MDA) 1 and 2-methyl-4,5-methylenedioxyamphetamine 3 with [C-11]CH3I. The radioche mical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-Il on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors 1 or 3, thus obtaining radioche mical yields of 60% (based on produced [C-11]CH3I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed fo r [C-11]MDMA in contrast to a ratio of 3.7 for [C-11]MADAM-6.