Life Sciences, Vol. 47, pp. 1955-1963 Printed in the U.S.A. PergamonPress zyxwvutsr MOUSE BRAIN DISTRIBUTION OF A CARBON-11 LABELED VESAMICOL DERIVATIVE: PRESYNAPTIC MARKER OF CHOLINERGIC NEURONS Michael R. Kilbourn*, Yong-Woon Jung, Michael S. Haka, David L. Gildersleeve, David E. Kuhl and Donald M. Wieland Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109 (Received in final form September 18, 1990) The regional mouse brain distribution of a new carbon-11 labeled derivative of vesamicol, [llC]-5(N-methylamino)benzovesamicol (IllCIMABV) is reported. Radiotracer concentrations in zyxwvutsrqponmlkjihgfedcba uiuo are in the rank order of striatum>cortex>hippocampus>hypothalamus> cerebellum, consistent with reported distributions of other presynaptic cholinergic neuronal markers. In time course studies, striatum/cerebellum and cortex/cerebellum ratios for (-)-[llClMABV continue to increase to values of 13 and 5, respectively, 75 min after i.v. injection of [llC]MABV. The specific binding in striatum and cortex is lowered by pretreatment with (+vesamicol, and shows stereoselectivity with lower uptake and lower ratios for the (+)-enantiomer. (->- [llC]MABV is proposed as a positron-emitting radioligand for the in uiuo study of presynaptic cholinergic neurons. Alzheimer’s disease is characterized by degeneration of the cholinergic neurotransmitter system. The unique biochemical characteristics of the cholinergic neuron, such as high affinity choline uptake (HAChU), choline acetyltransferase (ChAT), and vesicular storage of acetylcholine have been thoroughly studied in vitro using radiotracer or immunochermstry techniques. Declines in ChAT and HAChU, as well as in acetylcholmesterase, are now widely recognized features of the neurochemical pathology in Alzheimer’s disease (1,2,3). Radiotracers which mark specific presynaptic biochemical processes of cholinergic neurons might be useful for assessment of changes in function or number of such terminals rn uiuo using positron emission tomography (PET). Vesamicol (2-(4-phenylplperidino)cyclohexanol: AH5183) binds to a specific site on presynaptic acetylcholine storage vesicles where it acts as a stereoselective, non-competitive, allosteric inhibitor of acetylcholine uptake into the vesicle (4,5,6). We have prepared a high specific activity, carbon-11 (p+, ty2 = 20.4 min> labeled derivative of vesamicol, (N-([llClmethyl)-aminobenzovesamicol ([llC]MABV), and report here preliminary in wuo biodistribution results in mouse brain. 0024-3205190 $3.00 +.oo Copyright (c) 1990 Pergamon Press plc