IN-VIVO IMAGING OF HUMAN CEREBRAL ACETYLCHOLINESTERASE

We report here the first positron emission tomography (PET) images sho wing the in vivo regional distribution of acetylcholinesterase (AChE) in human brain. The study was carried out in eight healthy human volun teers using as a tracer [C-11]physostigmine ([C-11]PHY), an inhibitor of AChE. After intravenous injection of [C-11]PHY, radioactivity was r apidly taken up in brain tissue and reached maximal uptake within a fe w minutes, following a regional pattern mostly related to cerebral per fusion. After the peak, the cerebral radioactivity gradually decreased with a half-life varying from 20 to 35 min, depending on the brain st ructure. [C-11]PHY retention was higher in regions rich in AChE, such as the striatum (half-life, 35 min), than in regions poor in AChE, suc h as the cerebral cortex (half-life, 20 min). At later times (25-35 mi n postinjection), the cerebral distribution of [C-11]PHY was typical o f AChE activity: putamen-caudate > cerebellum > brainstem > thalamus > cerebral cortex, with a striatal to cortex ratio of 2. These results suggest that PET studies with [C-11] PHY can provide in vivo brain map ping of human AChE and are promising for the study of changes in AChE levels associated with neurodegenerative diseases.