title: In vivo PET study of cerebral [11C] methyl- tetrahydroaminoacridine distribution and kinetics in healthy human subjects.
abstract: It is unclear whether the palliative effects of tetrahydroaminoacridine (THA) (tacrine, Cognex) on the clinical symptoms of patients affected by Alzheimer's disease (AD) are the result of its inhibitory activity on acetylcholinesterase or on other complex sites of action. In order to investigate the cerebral distribution and kinetics of THA in the human brain in vivo, we performed positron emission tomography (PET) imaging with [11C]N-methyl-tetrahydro-aminoacridine (MTHA) in healthy human volunteers. After intravenous injection, [11C]MTHA crossed the blood-brain barrier and reached its maximum uptake between 10 and 40 minutes, depending on the brain regions. Uptake was higher in the grey matter structures, and lower in the white matter. After this peak, the radioactivity remained quasi- constant until 60 minutes in all regions with a half-life varying from 2.44 hours in the thalamus to 3.42 hours in the cerebral cortex. The ratios of regional to whole cerebral cortex brain radioactivity calculated between 50 and 70 minutes after the tracer injection were 1.14 +/- 0.04, 1.07 +/- 0. 03 and 1.06 +/- 0.04 in the putamen, cerebellum and thalamus, respectively. Overall, these results show that: (1) [11C]MTHA crosses the blood-brain barrier easily and is highly concentrated in the brain; (2) the regional brain distribution of [11C]MTHA does not parallel that of in vivo acetylcholinesterase (AChE) concentrations; and (3) the cerebral kinetics of [11C]MTHA are consistent with known plasmatic pharmacokinetics of THA in AD patients. We conclude that PET imaging with [11C]MTHA is a useful method for assessing the cerebral distribution and kinetics of THA in vivo.
authors.affiliation: 1 INSERM Unit 334, Service Hospitalier Frederic Joliot, CEA/DSV/DRM, Orsay, France and INSERM Unit 324, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Traykov
authors.forename: B
authors.initials: B
authors.lastname: Tavitian
authors.forename: A
authors.initials: A
authors.lastname: Jobert
authors.forename: F
authors.initials: F
authors.lastname: Boller
authors.forename: F
authors.initials: F
authors.lastname: Forette
authors.forename: C
authors.initials: C
authors.lastname: Crouzel
authors.forename: L
authors.initials: L
authors.lastname: Di Giamberardino
authors.forename: S
authors.initials: S
authors.lastname: Pappata
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D013619:Tacrine / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D013619:Tacrine