C-11 LABELING OF AN INHIBITOR OF ACETYLCHOLINESTERASE - [C-11] PHYSOSTIGMINE

Physostigmine, an alkaloid from calabar bean is a strong inhibitor of acetylcholinesterase (Ki=3.33+/-0.26x10(-6)M) and has been used clinically in the treatment of glaucoma, atropine intoxication, myasthenia gravis and more recently, in experimental trials in Alzheimer's disease. In order to study the AChE activity in the brain by positron emission tomography, we have undertaken the labelling of physostigmine with carbon-11. The synthesis involves the reaction of [C-11]methylisocyanate with eseroline. [C-11]Methylisocyanate was obtained by heating [C-11]acetylchloride with tetrabutylammonium azide in toluene. The synthesis of [C-11]CH3COCl involves the carbonation of methylmagnesium bromide in THF with cyclotron produced [C-11]carbon dioxide and the addition of phthaloyl dichloride. The [C-11]methylisocyanate is distilled into a solution of eseroline in ether with a small piece of sodium. After 10 minutes at 25-degrees-C, the solution is purified by HPLC and the appropriate fraction collected. Starting with 55.5 GBq (1.5 Ci) of [C-11]carbon dioxide, 0.92-1.48 GBq (25-40 mCi) of [C-11]Physostigmine are obtained 57 minutes after EOB.