Synthesis of 1-[11C]methylpiperidin-4-yl propionate ([11C]PMP) for in vivo measurements of acetylcholinesterase activity.
Synthesis of 1-[11C]methylpiperidin-4-yl propionate ([11C]PMP), an in vivo substrate for acetylcholinesterase, is reported. An improved preparation of 4-piperidinyl propionate (PHP), the immediate precursor for radiolabeling, was accomplished in three steps from 4-hydroxypiperidine by (a) protection of the amine as the benzyl carbamate, (b) acylation 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 [11C]methyl trifluoromethanesulfonate at room temperature in N,N-dimethylformamide, followed by high performance liquid chromatography (HPLC) purification, provided [11C]PMP in 57% radiochemical yield, > 99% radiochemical purity, and > 1500 Ci/mmol at the end of synthesis. The total synthesis time from end-of-bombardment was 35 min. [11C]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography.
Snyder
S E
SE
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028, USA. snyderse@umich.edu
Tluczek
L
L
Jewett
D M
DM
Nguyen
T B
TB
Kuhl
D E
DE
Kilbourn
M R
MR
D000110:Acetylcholinesterase / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology*; D002250:Carbon Radioisotopes; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004126:Dimethylformamide; D006801:Humans; D006865:Hydrogenation; D007553:Isotope Labeling; D008698:Mesylates; D011422:Propionates / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D008698:Mesylates; D011422:Propionates; D019275:Radiopharmaceuticals; C078465:methyl triflate; C099183:N-methylpiperidin-4-yl propionate; D004126:Dimethylformamide; D000110:Acetylcholinesterase