In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model |
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| Authors: | Dr Thomas Le Bihan Dr Cathryn H S Driver Dr Thomas Ebenhan Dr Nathalie Le Bris Dr Jan Rijn Zeevaart Prof?Dr Raphaël Tripier |
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| Affiliation: | 1. UMR CNRS 6521 CEMCA, University of Brest, 6 avenue Le Gorgeu, CS93837, 29200 Brest, France;2. South African Nuclear Energy Corporation Radiochemistry and NuMeRI PreClinical Imaging Facility, Elias Motsoaledi Street, R104 Pelindaba, North West, 0240 South Africa |
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| Abstract: | An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2Mal, has been synthesized and studied for in vivo 64Cu-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. 64Cu]Cu-GluCAB-2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of 64Cu]Cu-GluCAB-2Mal and previous-generation 64Cu]Cu-GluCAB-1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of 64Cu]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 64Cu]Cu-Glu-CAB-2Mal. |
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| Keywords: | 64Cu PET cyclam EPR effect TE3A tumor targeting |
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