Bioorthogonal Masking of Circulating Antibody-TCO Groups Using Tetrazine-Functionalized Dextran Polymers.

ABSTRACT: Pretargeting strategies have gained popularity for the in vivo imaging and therapy of cancer by combining antibodies with small molecule radioligands. In vivo recombination of both moieties can be achieved using the bioorthogonal inverse electron demand Diels-Alder (IEDDA) chemistry between tetrazine (Tz) and trans-cyclooctene (TCO). An issue that arises with pretargeting strategies is that while part of the antibody dose accumulates at antigen-expressing tumor tissue, there is a significant portion of the injected antibody that remains in circulation, causing a reduction in target-to-background ratios. Herein, we report the development of a novel TCO scavenger, the masking agent DP-Tz. DP-Tz is based on Tz-modified dextran polymers (DP, MW = 0.5-2 MDa). Large dextran polymers were reporte

SUBMITTER: Meyer JP 

PROVIDER: S-EPMC6004324 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature