biostudies-literatureUnknown13(26)Rodriguez CWe report the <i>in vitro</i> characterization and <i>in vivo</i> evaluation of a novel ⁸⁹Zr-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 <i>trans</i>-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-^SPOCQhuA33) with equivalent antigen binding affinity to its parent immunoglobulin but attenuated affinity for the FcγRI receptor. This construct was subsequently radiolabeled with [⁸⁹Zr]Zr⁴⁺ to create a radioimmunoconjugate - [⁸⁹Zr]Zr-DFO-^SPOCQhuA33 - in high yield and specific activity that exhibited excellent <i>in vivo</i> behavior in two murine models of human colorectal carcinoma.RSC advances17705-17709https://www.ebi.ac.uk/biostudies/studies/S-EPMC10258682biostudies-literatureSite-selective radiolabeling using mushroom tyrosinase and the strain-promoted oxidation-controlled 1,2-quinone cycloaddition.PMC10258682Hosny MMThau SDelaney SRodriguez CSarrett SMCornejo MASebastiano JZeglis BMfalseSite-selective radiolabeling using mushroom tyrosinase and the strain-promoted oxidation-controlled 1,2-quinone cycloaddition.We report the <i>in vitro</i> characterization and <i>in vivo</i> evaluation of a novel ⁸⁹Zr-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 <i>trans</i>-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-^SPOCQhuA33) with equivalent antigen binding affinity to its parent immunoglobulin but attenuated affinity for the FcγRI receptor. This construct was subsequently radiolabeled with [⁸⁹Zr]Zr⁴⁺ to create a radioimmunoconjugate - [⁸⁹Zr]Zr-DFO-^SPOCQhuA33 - in high yield and specific activity that exhibited excellent <i>in vivo</i> behavior in two murine models of human colorectal carcinoma.2023-01-01T00:00:00Z2023 Jun2025-04-26T09:42:43.165Z2025-04-26T09:42:43.165ZS-EPMC102586823731300010.1039/d3ra03486k