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

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 penetration. The addition of an alkyl carboxylate ester pendant arm offers high binding affinity toward Cu(II). The novel BFCs form stable ⁶⁴ Cu-radiolabeled complexes and exhibit promising partition coefficient (log D ) values of 1.05-1.85. Among the five compounds tested, the ⁶⁴ Cu-YW-15 complex exhibits significant staining of amyloid β plaques in ex vivo autoradiography studies. In addition, biodistribution studies show that ⁶⁴ Cu-YW-15-Me exhibits moderate brain uptake (0.69 ± 0.08 %ID/g) in wild type mice.