Fluorine-18 and carbon-11 labeled amphetamine analogs—Synthesis, distribution, binding characteristics in mice and rats and a PET study in monkey

摘要: No-carrier-added (NCA) (+-)-p-[18F]fluoroamphetamine (2a) and (+-)-6-[18F]fluoro-3,4-methylene-dioxy-amphetamine (2b) were synthesized through a multistep synthesis by nucleophilic substitution of the appropriate precursors (p-nitrobenzaldehyde, 1a 6-nitropiperonal 1b, respectively) with [18F]fluoride followed condensation nitroethane reduction LAH in 20-30% yield (EOB) time 90-109 min from EOB. NCA (-)-[11C]methamphetamine (4a) (+-)-3,4-methylene-dioxy-N-[11C]methamphetamine (4b) methylation desmethyl 3a 3b [11C]H3I 40-60% 30 Animal studies mouse rat revealed that relative tissue uptake these radiotracers was kidneys > lungs liver spleen brain heart blood. The uptakes high similar at 5 post-injection (approx. 5%/g) but radioactivity then declined rapidly 1%/g 60 post-injection). For compounds 2a 2b, activity femur did not increase indicating vivo defluorination may be major route metabolism. Monoamine inhibitors (nomifensine, fluoxetine nisoxetine) inhibit enhance greater than 50%. A PET study Rhesus monkey different regions retention remained constant throughout study. Analysis arterial plasma HPLC showed 50% as 4a post-injection.