RADIOSYNTHESIS OF [C-11] BROFAROMINE, A POTENTIAL TRACER FOR IMAGING MONOAMINE-OXIDASE-A

-5(-methoxy-7-bromobenzofuranyl)-2-piperidine-HCl) is a potent and sel ective inhibitor of monoamine oxidase (MAO) A. Two methods for its syn thesis and a preliminary positron emission tomography (PET) evaluation in monkey brain are described. The first method, at low carrier conce ntration of CO2, consisted of direct O-methylation of (4-(5-hydroxy-7- bromobenzofuranyl) 2-piperidine). The total radiochemical yield achiev ed ranged from 30 to 50% (from end of bombardment [EOB] and decay corr ected) with an overall synthesis time of 45 min, The second approach, with high carrier amounts of CO2 arising from inherent target problems , was accomplished in a three-step route involving protection of secon dary amino functionality, O-methylation and deprotection. The total ra diochemical yield was 10% (from EOB and decay corrected) with a total synthesis time of 70 min, For both methods methylation was achieved us ing the classical methylating agent [C-11]CH3I, and radiochemical puri ty was higher than 98%. PET evaluation of the radioligand in a Rhesus monkey showed a high uptake of radioactivity in the brain. Using the i rreversible MAO-A inhibitor clorgyline and reversible MAO-A inhibitors moclobemide and brofaromine, three blockade experiments were designed to determine the extent of specific binding of [C-11]brofaromine to M AO-A. No apparent decrease in accumulation of radioactivity in the mon key brain was observed when compared to a baseline scan.