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In Vivo Albumin‐Binding of a C ‐Functionalized Cyclam Platform for 64 Cu‐PET/CT Imaging in Breast Cancer Model
Author(s) -
Le Bihan Thomas,
Driver Cathryn H. S.,
Ebenhan Thomas,
Le Bris Nathalie,
Zeevaart Jan Rijn,
Tripier Raphaël
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000800
Subject(s) - in vivo , radioligand , chemistry , biodistribution , breast cancer , cyclam , albumin , bovine serum albumin , cancer , cancer research , biochemistry , in vitro , medicine , biology , microbiology and biotechnology , organic chemistry , metal
An improved glucose‐chelator‐albumin bioconjugate (GluCAB) derivative, GluCAB‐2 Mal , 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‐1 Mal . 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‐2 Mal (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‐2 Mal and previous‐generation [ 64 Cu]Cu‐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 of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [ 64 Cu]Cu‐Glu‐CAB‐2 Mal .