Aromatic radiofluorination and biological evaluation of 2-aryl-6-[18F] fluorobenzothiazoles as a potential positron emission tomography imaging probe for β-amyloid plaques

To develop agents for radionuclide imaging Ab plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Ab (K-i = 5.5 nM) and the specific binding to Ab in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in radiolabeled form as an Ab 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) = 110 min) and diaryliodonium tosylate precursors (12, 13a-e and 14). 2-Aryl-6-[F-18]fluorobenzothiazoles ([F-18]1-3) were synthesized in efficiently short reaction times (40-60 min) with high radiochemical yields (19-40%), purities (> 95%) and specific activities (85-118 GBq/mu mol). Tissue distribution studies showed that high radioactivity of [F-18]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 30 min after a tail-vein injection. These results suggest that [F-18] 2 is a promising probe for evaluation of Ab plaques imaging in brain using PET. (C) 2011 Elsevier Ltd. All rights reserved.