Design and synthesis of astatinated benzothiazole compounds for their potential use in Targeted Alpha Therapy (TAT) strategies to treat Alzheimer's disease-associated amyloid plaques

Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer. Benzothiazole derivatives have been successfully shown to target these plaques and are used in several imaging applications. One such derivative, Flutemetamol (VizamylTM) is an FDA approved diagnostic tool for PET imaging of AD-associated plaques. We report the radiolabeling of benzothiazole derivatives with 211At, a 7.2 h alpha emitting radionuclide, using a copper catalyzed reaction with a boronic acid precursor molecule. Our final compound [211At]3′-At-PIB-OMe had a radiochemical yield of 55% and was found to be stable for at least 3 h in phosphate buffered saline. •Iodination and astatination with boronic acid precursors.•Synthesis of an astatinated benzothiazole derivatives for the potential treatment of amyloid diseases such as Alzheimer's Disease.•Radiolabeled [211At]3′-At-PIB-OMe with 55% RCY.•[211At]3′-At-PIB-OMe showed greater than 99% radiochemical stability in 3 h in a 50:50 mixture of MeOH and PBS.