Synthesis, in vivo biodistribution and dosimetry of [11C]N-methylpiperidyl benzilate ([11C]NMPB), a muscarinic acetylcholine receptor antagonist.
4-N-Methylpiperidyl benzilate (NMPB), a high affinity antagonist for the muscarinic cholinergic receptor, has been synthesized in carbon-11-labeled form through the N-[11C]methylation of 4-piperidylbenzilate. The product was isolated by HPLC, and obtained in yields (> 100 mCi) and specific activities (500-3000 Ci/mmol) sufficient for in vivo evaluation in small animals. Time-dependent regional brain distributions in rats and mice showed high radiotracer uptake and retention in striatum and cortex, and low in cerebellum, consistent with muscarinic cholinergic receptor distributions. Radiotracer retention in tissues could be significantly reduced by pretreatment of animals with a large dose of a competing antagonist, quiniclidinyl benzilate. Whole body biodistribution in rats was used to calculate the expected human internal radiation dosimetry for this new radiopharmaceutical. These animal experiments formed the basis for subsequent introduction of [11C]NMPB into human use with positron emission tomography.
Mulholland
G K
GK
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109, USA.
Kilbourn
M R
MR
Sherman
P
P
Carey
J E
JE
Frey
K A
KA
Koeppe
R A
RA
Kuhl
D E
DE
D000818:Animals; D001561:Benzilates / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D005260:Female; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000138:chemical synthesis*; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011829:Radiation Dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D001561:Benzilates; D002250:Carbon Radioisotopes; D018727:Muscarinic Antagonists; D010880:Piperidines; C020407:enpiperate