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 = 5.5 nM) 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 = 110 min) and diaryliodonium tosylate precursors ( 12, 13a– e and 14). 2-Aryl-6-[ 18F]fluorobenzothiazoles ([ 18F] 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/μmol). Tissue distribution studies showed that high radioactivity of [ 18F] 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 [ 18F] 2 is a promising probe for evaluation of Aβ plaques imaging in brain using PET.