2-[18F]F-A-85380: a PET radioligand for alpha4beta2 nicotinic acetylcholine receptors.
2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380), a ligand for nicotinic acetylcholine receptors (nAChRs) was evaluated in an in vitro binding assay with membranes of rat brain and in vivo by PET in Rhesus monkey brain. The ligand has high affinity for alpha4beta2 nAChRs (K(D)=50 pM), crosses the blood-brain barrier, and distributes in the monkey brain in a pattern consistent with that of alpha4beta2 nAChRs. The specific/non-specific binding ratio increased steadily, reaching a value of 3.3 in the thalamus at 4 h. The specific binding of 2-[18F]F-A-85380 was reversed by cytisine. These results, in combination with the data demonstrating low toxicity of 2-[18F]F-A-85380, indicate that this ligand shows promise for use with PET in human subjects.
Chefer
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Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Horti
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Koren
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Gündisch
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Kurian
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Dannals
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Mukhin
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London
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D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001384:Azetidines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D001392:Azocines; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D008024:Ligands; D008253:Macaca mulatta; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D011807:Quinolizines; D019275:Radiopharmaceuticals / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism; D013997:Time Factors; D014055:Tomography, Emission-Computed; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001384:Azetidines; D001392:Azocines; D008024:Ligands; D011725:Pyridines; D011807:Quinolizines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; C004712:cytisine; D000093843:Quinolizidine Alkaloids