Benzothiazole Carboxylate Diester Bifunctional Chelators for 64Cu PET Imaging in Alzheimer’s Disease

Abstract

Herein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid β aggregates, strong binding affinity towards Cu(II), and favorable lipophilicity for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate ester pendant arms enable high binding affinity towards Cu(II). The BFCs form stable <sup>64</sup>Cu-radiolabeled complexes and exhibit favorable partition coefficient (log D) values of 0.75-0.95. Among the five compounds tested, the <b><sup>64</sup>Cu-YW-1</b> and <b><sup>64</sup>Cu-YW-13</b> complexes exhibit significant staining of amyloid plaques in <i>ex vivo</i> autoradiography studies.