Characterization of 64Cu-DOTA-Conatumumab: A PET Tracer for In Vivo Imaging of Death Receptor 5

Conatumumab is a fully human monoclonal antibody that binds to and activates human death receptor 5 (DR5; also known as TRAIL receptor 2). The purpose of this study was to character-ize 64Cu-labeled conatumumab as a PET tracer for imaging DR5 in tumors. Methods: DOTA-conatumumab was synthesized by incubating conatumumab with 2,29,2$-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA-NHS). The absolute numbers of DOTA molecules per conatumumab molecules were determined by matrix-assisted laser desorption ionization mass spectrometry and electrospray ionization quadrupole time-of-flight mass spectrometry. 64Cu-DOTA-conatumumab was prepared by incubating 64CuCl2 (33–222 MBq) with DOTA-conatumumab at 37C for 1 h. Binding of conatumumab and DOTA-conatu-mumab to Fc-coupled human DR5 (huTR2-Fc) was tested i