Comparative PET studies of the distribution of (-)-3,4-methylenedioxy-N-[¹¹C]methamphetamine and (-)-[¹¹C]methamphetamine in a monkey brain

Carbon-11 labeled (-)-methamphetamine and (-)-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [¹¹C]H₃I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/μM. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of (-)-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as (-)-methamphetamine while only 3% remained as (-)-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes.