title: Aromatic radiofluorination and biological evaluation of 2-aryl-6-[18F]fluorobenzothiazoles as a potential positron emission tomography imaging probe for β-amyloid plaques.
abstract: To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (K(i)=5.5nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in radiolabeled form as an Aβ plaques-specific positron emission tomography (PET) imaging probe, we investigated synthetic route suitable for its labeling with the short-lived PET radionuclide fluorine-18 (t(1/2)=110min) and diaryliodonium tosylate precursors (12, 13a-e and 14). 2-Aryl-6-[(18)F]fluorobenzothiazoles ([(18)F]1-3) were synthesized in efficiently short reaction times (40-60min) with high radiochemical yields (19-40%), purities (>95%) and specific activities (85-118GBq/μmol). Tissue distribution studies showed that high radioactivity of [(18)F]2 accumulated in the brain with rapid clearance in healthy mice. Radioactive metabolites were analyzed in brain samples of mice and corresponded to 81% of parent remained by 30min after a tail-vein injection. These results suggest that [(18)F]2 is a promising probe for evaluation of Aβ plaques imaging in brain using PET.
authors.affiliation: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Bom Sahn
authors.initials: BS
authors.lastname: Kim
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Son
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Hong
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Moon
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Jung
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: C560383:2-(4'-methylaminophenyl)-6-fluorobenzothiazole; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals