In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64 Cu-PET/CT Imaging in Breast Cancer Model.

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2Mal , has been synthesized and studied for in vivo 64 Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1Mal . The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [64 Cu]Cu-GluCAB-2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64 Cu]Cu-GluCAB-2Mal and previous-generation [64 Cu]Cu-GluCAB-1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64 Cu]Cu-GluCAB-2Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [64 Cu]Cu-Glu-CAB-2Mal .