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

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