Work

Divalent 2-(4-Hydroxyphenyl)benzothiazole Bifunctional Chelators for 64 Cu Positron Emission Tomography Imaging in Alzheimer’s Disease

Year: 2022

Type: article

Abstract: Herein we report a new series of divalent 2-(4-hydroxyphenyl)benzothiazole bifunctional chelators (BFCs) with high affinity for amyloid β aggregates and favorable lipophilicity for blood-brain barrier (BBB) penetration. The addition of an alkyl carboxylate ester pendant arm offers high binding affinity towards Cu(II). The novel BFCs form stable 64Cu-radiolabeled complexes and exhibit promising partition coefficient (log D) values of 1.05-1.85. Among the five compounds tested, the 64Cu-YW-15 complex exhibits significant staining of amyloid β plaques in ex vivo autoradiography studies. In addition, biodistribution studies show that 64Cu-YW-15-Me exhibits elevated brain uptake (0.89 ± 0.25 %ID/g) in transgenic AD versus wild type mice.

Source: Inorganic Chemistry

DOI: 10.1021/acs.inorgchem.2c02740