Formula omitted]: The radioligand of choice for pett studies of the dopamine receptor in human brain

Abstract

N-methylspiroperidol, the amide N-methyl analogue of the neuroleptic spiroperidol, was radiolabeled with fluorine-18, and its distribution in the baboon brain was studied using positron emission transaxial tomography. Stereospecific binding was demonstrated in the striatum (but not in the cerebellum) by pretreatment with (-)- or (+)-butaclamol. The kinetic distribution was similar to that of [ 18F]spiroperidol, but the absolute striatal uptake (in percent of administered dose) was at least two-fold higher. Analysis of baboon blood at 10 min after injection indicated that less than half of the radioactivity in the plasma was due to unchanged radioligand. Analysis of the metabolic stability of [ 18 F]-N- methylspiroperidol in rat brain for 4 hr indicated that, like [ 18F]spiroperidol, it is very stable to metabolic transformation in the rat central nervous system. Striatal uptake and retention in the rat was five-fold higher for [ 18 F]-N- methylspiroperidol than for [ 18F]spiroperidol. These results suggest that [ 18 F]-N- methylspiroperidol is an ideal choice for studies of the dopamine receptor in humans.