Synthesis and autoradiographic localization of muscarinic cholinergic antagonist (+) N-[ 11C]methyl-3-piperidyl benzilate as a potent radioligand for positron emission tomography

• Published in: Applied radiation and isotopes 1999-03, Vol.50 (3), p.521-525
• Main Authors: Takahashi, Kazuhiro, Murakami, Matsutaro, Miura, Shuichi, Iida, Hidehiro, Kanno, Iwao, Uemura, Kazuo
• Format: Article
• Language: English
• Subjects: Animals; Aromatic compounds; Autoradiography; Benzilates - chemical synthesis; Benzilates - chemistry; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes; Chemical bonds; Magnetic Resonance Spectroscopy; Male; Medical imaging; Muscarinic Antagonists - chemical synthesis; Muscarinic Antagonists - chemistry; Positron emission tomography; Radioactivity; Radioligand Assay; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic - metabolism; Synthesis (chemical); Tissue Distribution; Tomography, Emission-Computed - methods
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/S0969-8043(97)10155-5

(+) N-[ 11C]methyl-3-piperidyl benzilate, a relatively low affinity muscarinic cholinergic receptor antagonist was synthesized by N-[ 11C]methylation of (+)3-piperidyl benzilate using [ 11C]methyl iodide. The product was isolated by HPLC, and obtained with radiochemical yield of 60–70% from [ 11C]methyl iodide, and a specific activity of 500–1000 Ci mmol −1 (18.5–37 GBq μmol −1) at EOS and radiochemical purity of >98%. In vitro autoradiographic studies showed selective binding for this radiotracer in the different regions of the rat brain: high in corpus striatum, hippocampus and cerebral cortex, and low in cerebellum, consistent with muscarinic cholinergic receptor distributions. This radiotracer thus had potential as radioligand for positron emission tomography.