6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors.
A novel positron emission tomography (PET) radiotracer, 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380, 6-[18F]FA) was synthesized by a no-carrier-added fluorination. In vitro 6-[18F]FA bound to nicotinic acetylcholine receptors (nAChRs), with very high affinity (Kd 28 pM). In PET studies, 6-[18F]FA specifically labeled central nAChRs in the brain of the Rhesus monkey and demonstrated highest levels of accumulation of radioactivity in brain regions enriched with the alpha4beta2 subtype of nAChR. 6-[18F]FA exhibited a target-to-non-target ratio (estimated as radioactivity in the thalamus to that in the cerebellum) of binding in primate brain similar to that previously determined for a labeled analog of epibatidine, [18F]FPH. In contrast to [18F]FPH, the novel tracer is expected to exhibit substantially less toxicity. Thus, the novel radioligand, 6-[18F]FA, appears to be a suitable candidate for imaging nAChRs in human brain.
Horti
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AG
Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Chefer
S I
SI
Mukhin
A G
AG
Koren
A O
AO
Gündisch
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Links
J M
JM
Kurian
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Dannals
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RF
London
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D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011978:Receptors, Nicotinic / Q000032:analysis*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
C104288:A 85380; D001384:Azetidines; D005462:Fluorine Radioisotopes; D011978:Receptors, Nicotinic