Enzyme-mediated methodology for the site-specific radiolabeling of antibodies based on catalyst-free click chemistry Journal Article
| Authors: | Zeglis, B. M.; Davis, C. B.; Aggeler, R.; Kang, H. C.; Chen, A.; Agnew, B. J.; Lewis, J. S. |
| Article Title: | Enzyme-mediated methodology for the site-specific radiolabeling of antibodies based on catalyst-free click chemistry |
| Abstract: | An enzyme- and click chemistry-mediated methodology for the site-selective radiolabeling of antibodies on the heavy chain glycans has been developed and validated. To this end, a model system based on the prostate specific membrane antigen-targeting antibody J591, the positron-emitting radiometal 89Zr, and the chelator desferrioxamine has been employed. The methodology consists of four steps: (1) the removal of sugars on the heavy chain region of the antibody to expose terminal N-acetylglucosamine residues; (2) the incorporation of azide-modified N-acetylgalactosamine monosaccharides into the glycans of the antibody; (3) the catalyst-free click conjugation of desferrioxamine-modified dibenzocyclooctynes to the azide-bearing sugars; and (4) the radiolabeling of the chelator-modified antibody with 89Zr. The site-selective labeling methodology has proven facile, reproducible, and robust, producing 89Zr-labeled radioimmunoconjguates that display high stability and immunoreactivity in vitro (>95%) in addition to highly selective tumor uptake (67.5 ± 5.0%ID/g) and tumor-to-background contrast in athymic nude mice bearing PSMA-expressing subcutaneous LNCaP xenografts. Ultimately, this strategy could play a critical role in the development of novel well-defined and highly immunoreactive radioimmunoconjugates for both the laboratory and clinic. © 2013 American Chemical Society. |
| Keywords: | human cell; nonhuman; mouse; animal experiment; animal model; in vitro study; immunoreactivity; monoclonal antibody j591; isotope labeling; xenograft; zirconium; deferoxamine; click chemistry; glycan; n acetylglucosamine; azide; n acetylgalactosamine; heavy chain |
| Journal Title: | Bioconjugate Chemistry |
| Volume: | 24 |
| Issue: | 6 |
| ISSN: | 1043-1802 |
| Publisher: | American Chemical Society |
| Date Published: | 2013-06-19 |
| Start Page: | 1057 |
| End Page: | 1067 |
| Language: | English |
| DOI: | 10.1021/bc400122c |
| PROVIDER: | scopus |
| PMCID: | PMC3714844 |
| PUBMED: | 23688208 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2013" - "CODEN: BCCHE" - "Source: Scopus" |
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