SYNTHESIS OF 1-[C-11]METHYLPIPERIDIN-4-YL PROPIONATE ([C-11]PMP) FOR IN-VIVO MEASUREMENTS OF ACETYLCHOLINESTERASE ACTIVITY

Synthesis of 1-[C-11]methyipiperidin-4-yl propionate ([11C]PMP), an in vivo substrate for acetylcholinesterase, is reported. An improved pre paration of 4-piperidinyl propionate (PHP), the immediate precursor fo r radiolabeling, was accomplished in three steps from 4-hydroxypiperid ine by (a) protection of the amine as the benzyl carbamate, (b) acylat ion with propionyl chloride, and (c) deprotection of the carbamate by catalytic hydrogenation. The final product was obtained in an overall 82% yield. Reaction of the free base form of PHP with [C-11]methyl tri fluoromethanesulfonate at room temperature in N,N-dimethylformamide, f ollowed by high performance liquid chromatography (HPLC) purification, provided [C-11]PMP in 57% radiochemical yield, >99% radiochemical pur ity, and >1500 Ci/mmol at the end of synthesis. The total synthesis ti me from end-of-bombardment was 35 min. [C-11]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography. NUCL MED BIOL 25;8:751-754, 1998. (C) 1998 Elsevier Science Inc.