6-[ 18F]fluoro-A-85380: an in vivo tracer for the nicotinic acetylcholine receptor

• Published in: Nuclear medicine and biology 2000, Vol.27 (1), p.51-56
• Main Authors: Scheffel, Ursula, Horti, Andrew G, Koren, Andrei O, Ravert, Hayden T, Banta, Jeffrey P, Finley, Paige A, London, Edythe D, Dannals, Robert F
• Format: Article
• Language: English
• Subjects: 6-[ 18F]FA; A-85380 derivative; Animals; Azetidines - chemical synthesis; Azetidines - metabolism; Azetidines - pharmacokinetics; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Fluorine Radioisotopes; Injections, Subcutaneous; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Mice; Mice, Inbred ICR; Mouse brain distribution; Nervous system; Nicotinic acetylcholine receptor (nAChR); PET; Radiochemistry; Radionuclide investigations; Radiotracer; Receptors, Nicotinic - metabolism; Tissue Distribution; Tomography, Emission-Computed
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(99)00082-7

6-[ 18F]Fluoro-3-(2( S)-azetidinylmethoxy)pyridine (6-[ 18F]fluoro-A-85380 or 6-[ 18F]FA), a new tracer for positron emission tomography, was synthesized by no-carrier-added [ 18F] fluorination of 6-iodo-3-((1- tert-butoxycarbonyl-2( S)-azetidinyl)methoxy)pyridine followed by acidic deprotection. 6-[ 18F]FA followed the regional densities of brain nicotinic acetylcholine receptors (nAChRs) reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 6-FA. A preliminary toxicology study of the 6-FA showed a relatively low biological effect.