In vivo PET study of cerebral [C-11] methy-tetrahydroaminoacridine distribution and kinetics in healthy human subjects

It is unclear whether the palliative effects of tetrahydroaminoacridine (TH A) (tacrine, Cognex) on the clinical symptoms of patients affected by Alzhe imer's disease (AD) are the result of its inhibitory activity on acetylchol inesterase 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 p erformed positron emission tomography (PET) imaging with [C-11]N-methyl-tet rahydro-aminoacridine (MTHA) in healthy human volunteers. After intravenous injection, [C-11]MTHA crossed the blood-brain barrier and reached its maxi mum uptake between 10 and 40 minutes, depending on the brain regions. Uptak e 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 cerebra l 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 th e putamen, cerebellum and thalamus, respectively. Overall, these results sh ow that: (1) [C-11]MTHA crosses the blood-brain barrier easily and is highl y concentrated in the brain; (2) the regional brain distribution of [C-11]M THA does not parallel that of in vivo acetylcholinesterase (AChE) concentra tions; and (3) the cerebral kinetics of [C-11]MTHA are consistent with know n plasmatic pharmacokinetics of THA in AD patients. We conclude that PET im aging with [C-11]MTHA is a useful method for assessing the cerebral distrib ution and kinetics of THA in vivo. Eur J Neurol 6:273-278 (C) 1999 Lippinco tt Williams & Wilkins.