Click-to-Release: Cleavable Radioimmunoimaging with [⁸⁹Zr]Zr-DFO-Trans-Cyclooctene-Trastuzumab Increases Tumor-to-Blood Ratio.

ABSTRACT: One of the main challenges of PET imaging with ⁸⁹Zr-labeled monoclonal antibodies (mAbs) remains the long blood circulation of the radiolabeled mAbs, leading to high background signals, decreasing image quality. To overcome this limitation, here we report the use of a bioorthogonal linker cleavage approach (click-to-release chemistry) to selectively liberate [⁸⁹Zr]Zr-DFO from trans-cyclooctene-functionalized trastuzumab (TCO-Tmab) in blood, following the administration of a tetrazine compound (trigger) in BT-474 tumor-bearing mice. Methods: We created a series of TCO-DFO constructs and evaluated their performance in [⁸⁹Zr]Zr-DFO release from Tmab in vitro using different trigger compounds. The in vivo behavior of the best perform

SUBMITTER: Vlastara M 

PROVIDER: S-EPMC10405837 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature