An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2 , has been synthesized and studied for in vivo Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1 . 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. [ Cu]Cu-GluCAB-2 (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [ Cu]Cu-GluCAB-2 and previous-generation [ Cu]Cu-GluCAB-1 encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [ Cu]Cu-GluCAB-2 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 [ Cu]Cu-Glu-CAB-2 .
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