Novel hexadentate and pentadentate chelators for 64Cu-based targeted PET imaging

摘要

A series of new hexadentate and pentadentate chelators were designed and synthesized as chelators of ⁶⁴Cu. The new pentadentate and hexadentate chelators contain different types of donor groups and are expected to form neutral complexes with Cu(II). The new chelators were evaluated for complex kinetics and stability with ⁶⁴Cu. The new chelators instantly bound to ⁶⁴Cu with high labeling efficiency and maximum specific activity. All ⁶⁴Cu-radiolabeled complexes in human serum remained intact for 2 days. The ⁶⁴Cu-radiolabeled complexes were further challenged by EDTA in a 100-fold molar excess. Among the ⁶⁴Cu-radiolabeled complexes evaluated, ⁶⁴Cu-complex of the new chelator >E was well tolerated with a minimal transfer of ⁶⁴Cu to EDTA. ⁶⁴Cu-radiolabeled complex of the new chelator >E was further evaluated for biodistribution studies using mice and displayed rapid blood clearance and low organ uptake. ⁶⁴Cu-chelator >E produced a favorable in vitro and in vivo complex stability profiles comparable to ⁶⁴Cu complex of the known hexadentate NOTA chelator. The in vitro and in vivo data highlight strong potential of the new chelator >E for targeted PET imaging application.