1 research outputs found
A Bone-Seeking <i>trans</i>-Cyclooctene for Pretargeting and Bioorthogonal Chemistry: A Proof of Concept Study Using <sup>99m</sup>Tc- and <sup>177</sup>Lu-Labeled Tetrazines
A high yield synthesis
of a novel, small molecule, bisphosphonate-modified <i>trans</i>-cyclooctene (TCO-BP, <b>2</b>) 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 <sup>99m</sup>Tc-labeled derivative
of <b>2</b> demonstrated selective localization to shoulder
and knee joints in a biodistribution study in normal mice. Compound <b>2</b> reacted rapidly with a <sup>177</sup>Lu-labeled tetrazine
in vitro, and pretargeting experiments in mice, using <b>2</b> and the <sup>177</sup>Lu-labeled tetrazine, yielded high activity
concentrations in shoulder and knee joints, with minimal uptake in
other tissues. Pretargeting experiments with <b>2</b> and a
novel <sup>99m</sup>Tc-labeled tetrazine also produced high activity
concentrations in the knees and shoulders. Critically, both radiolabeled
tetrazines showed negligible uptake in the skeleton and joints when
administered in the absence of <b>2</b>. Compound <b>2</b> can be utilized to target functionalized tetrazines to bone and
represents a convenient reagent to test novel tetrazines for use with
in vivo bioorthogonal pretargeting strategies