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 Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (Ki = 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 (t1/2 = 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.

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