POSITRON EMISSION TOMOGRAPHY STUDY OF [C-11] METHYL-TETRAHYDROAMINOACRIDINE (METHYL-TACRINE) IN BABOON BRAIN

THA (1,2,3,4-tetrahydro-9-amino-acridine, tacrine), a potential therap eutic agent for patients suffering from Alzheimer's disease, has multi ple pharmacological sites of action in the brain. In order to study th e cerebral binding sites of THA in vivo, we labeled a close derivative of THA with carbon 11 for positron emission tomography (PET) analysis . We report the biodistribution of this compound, 1,2,3,4-tetrahydro-9 -[C-11]methylaminoacridine ([C-11]MTHA), in the rodent and describe th e first PET experiments in non-human primates. The distribution of [C- 11]MTHA in baboon brain, although rather diffuse in the gray matter, s howed a higher concentration in the cortex and basal ganglia than in t he cerebellum and binding could be displaced (50%) by cold THA. These results suggest that [C-11]MTHA is a promising PET ligand for the stud y of the cerebral binding of THA.