A Bone-Seeking trans-Cyclooctene for Pretargeting and Bioorthogonal Chemistry: A Proof of Concept Study Using ^99mTc- and ¹⁷⁷Lu-Labeled Tetrazines.

ABSTRACT: A high yield synthesis of a novel, small molecule, bisphosphonate-modified trans-cyclooctene (TCO-BP, 2) that binds to regions of active bone metabolism and captures functionalized tetrazines in vivo, via the bioorthogonal inverse electron demand Diels-Alder (IEDDA) cycloaddition, was developed. A ^99mTc-labeled derivative of 2 demonstrated selective localization to shoulder and knee joints in a biodistribution study in normal mice. Compound 2 reacted rapidly with a ¹⁷⁷Lu-labeled tetrazine in vitro, and pretargeting experiments in mice, using 2 and the ¹⁷⁷Lu-labeled tetrazine, yielded high activity concentrations in shoulder and knee joints, with minimal uptake in other tissues. Pretargeting experiments with 2 and a novel ^99mTc-labeled tetrazine a

SUBMITTER: Yazdani A 

PROVIDER: S-EPMC6469506 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature