Site-selective radiolabeling using mushroom tyrosinase and the strain-promoted oxidation-controlled 1,2-quinone cycloaddition

Cindy Rodriguez; Samantha Delaney; Joni Sebastiano; Samantha M Sarrett; Mike A Cornejo; Sarah Thau; Meena M Hosny; Brian M Zeglis

doi:10.1039/d3ra03486k

Site-selective radiolabeling using mushroom tyrosinase and the strain-promoted oxidation-controlled 1,2-quinone cycloaddition

RSC Adv. 2023 Jun 12;13(26):17705-17709. doi: 10.1039/d3ra03486k. eCollection 2023 Jun 9.

Authors

Cindy Rodriguez^{1

2

3}, Samantha Delaney^{2

3

4}, Joni Sebastiano^{2

3

4}, Samantha M Sarrett^{2

3

4}, Mike A Cornejo^{1

2

3}, Sarah Thau², Meena M Hosny², Brian M Zeglis^{1

2

3

4

5}

Affiliations

¹ PhD Program in Chemistry, Graduate Center of the City University of New York New York New York 10016 USA bz102@hunter.cuny.edu.
² Department of Chemistry, Hunter College, City University of New York New York New York 10065 USA.
³ Department of Radiology, Memorial Sloan Kettering Cancer Center New York New York 10021 USA.
⁴ PhD Program in Biochemistry, Graduate Center of the City University of New York New York New York 10016 USA.
⁵ Department of Radiology, Weill Cornell Medical College New York New York 10021 USA.

Abstract

We report the in vitro characterization and in vivo 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 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-^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 in vivo behavior in two murine models of human colorectal carcinoma.

Abstract

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