Site-selective radiolabeling using mushroom tyrosinase and the strain-promoted oxidation-controlled 1,2-quinone cycloaddition.
Cindy RodriguezSamantha DelaneyJoni SebastianoSamantha M SarrettMike A CornejoSarah ThauMeena M HosnyBrian M ZeglisPublished in: RSC advances (2023)
We report the in vitro characterization and in vivo evaluation of a novel 89 Zr-labeled radioimmunoconjugate synthesized using a site-selective bioconjugation strategy based on the oxidation of tyrosinase residues exposed by the deglycosylation of the IgG and the subsequent strain-promoted oxidation-controlled 1,2-quinone cycloaddition between these amino acids and trans -cyclooctene-bearing cargoes. More specifically, we site-selectively modified a variant of the A33 antigen-targeting antibody huA33 with the chelator desferrioxamine (DFO), thereby producing an immunoconjugate (DFO- SPOCQ huA33) with equivalent antigen binding affinity to its parent immunoglobulin but attenuated affinity for the FcγRI receptor. This construct was subsequently radiolabeled with [ 89 Zr]Zr 4+ to create a radioimmunoconjugate - [ 89 Zr]Zr-DFO- SPOCQ huA33 - in high yield and specific activity that exhibited excellent in vivo behavior in two murine models of human colorectal carcinoma.