Synthesis of some 11C-labelled MAO-A inhibitors and their in vivo uptake kinetics in rhesus monkey brain

Five potential MAO-A inhibitors—harmine, N- methyl- harmine, harmaline, brofaromine, and clorgyline—were labelled with 11C and their brain kinetics evaluated in vivo in rhesus monkey using PET. The compounds were synthesized by alkylation with 11C methyl iodide and obtained in 48–89% radiochemical yield within 40 to 45 min synthesis time and with specific radioactivities in the region of 0.49–2.4 Ci μmol −1 (18–87 GBq μmol −1) at the end of synthesis. The kinetic pattern after administration of MAO-A inhibitors was comparable to that seen in the tracer study when using 11C-brofaromine, 11C-harmaline, or 11C-clorgyline, although the magnitude of uptake markedly increased in the case of brofaromine and harmaline. Both 11C-methylharmine and 11C-harmine showed a significant washout in the inhibition studies. The kinetics of brain uptake with and without MAO-A inhibition is compatible with a significant fraction of the tracer bound to MAO-A for 11C-methylharmine and 11C-harmine, whereas 11C-brofaromine, 11C-harmaline, or 11C-clorgyline did not seem to show specific enzyme binding.