2-(4-Hydroxyphenyl)benzothiazole dicarboxylate ester TACN chelators for 64Cu PET imaging in Alzheimer's disease

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

Automated summary

A new series of bifunctional chelators with high affinity for amyloid beta aggregates and strong binding affinity towards Cu(II) were reported, showing favorable lipophilicity for potential blood-brain barrier penetration. The compounds tested formed stable Cu-64-radiolabeled complexes with favorable partition coefficients, and two of them exhibited significant staining of amyloid plaques in ex vivo autoradiography studies.