Positron emission tomography study of [ 11C]methyl-tetrahydroaminoacridine (methyl-tacrine) in baboon brain

• Published in: European journal of pharmacology Vol. 236; no. 2; pp. 229 - 238
• Main Authors: Tavitian, Bertrand, Pappata, Sabina, Bonnot-Lours, Sophie, Prenant, Christian, Jobert, Antoinette, Crouzel, Christian, Di Giamberardino, Luigi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 19.05.1993; Elsevier
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Alzheimer's disease; Animals; Baboon; Binding Sites; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cholinesterase Inhibitors - pharmacology; Injections, Intravenous; Male; Medical sciences; Miscellaneous; Neuropharmacology; Papio; PET (positron emission tomography); Pharmacology. Drug treatments; Primates; Rat; Rats; Rats, Sprague-Dawley; Tacrine - analogs & derivatives; Tacrine - metabolism; Tacrine - pharmacokinetics; Tacrine - pharmacology; Tetrahydroaminoacridine (THA, tacrine); Tissue Distribution; Tomography, Emission-Computed; Tetrahydroaminoacridine (THA, tacrine); Rat; Acetylcholinesterase; Alzheimer's disease; PET (positron emission tomography); Baboon; Radionuclide study; Intravenous administration; Enzyme; Rodentia; Monkey; Enzyme inhibitor; Binding site; Vertebrata; Mammalia; Analog; Animal; Topography; Distribution; Primates; Pharmacokinetics; Positron emission tomography; Brain (vertebrata); Positron
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(93)90593-7

THA (1,2,3,4-tetrahydro-9-amino-acridine, tacrine), a potential therapeutic agent for patients suffering from Alzheimer's disease, has multiple pharmacological sites of action in the brain. In order to study the 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-[ 11C]methylaminoacridine ([ 11C]MTHA), in the rodent and describe the first PET experiments in non-human primates. The distribution of [ 11C]MTHA in baboon brain, although rather diffuse in the gray matter, showed a higher concentration in the cortex and basal ganglia than in the cerebellum and binding could be displaced (50%) by cold THA. These results suggest that [ 11C]MTHA is a promising PET ligand for the study of the cerebral binding of THA.