In Vivo Pretargeted Imaging of HER2 and TAG-72 Expression Using the HaloTag Enzyme

Molecular Pharmaceutics
James C KnightBart Cornelissen

Abstract

A novel pretargeted SPECT imaging strategy based on the HaloTag enzyme has been evaluated for the first time in a living system. To determine the efficacy of this approach, two clinically relevant cancer biomarkers, HER2 and TAG-72, were selected to represent models of internalizing and noninternalizing antigens, respectively. In MDA-MB-231/H2N (HER2-expressing) and LS174T (TAG-72-expressing) xenograft tumors in mice, pretargeting experiments were performed in which HaloTag-conjugated derivatives of the antibodies trastuzumab (anti-HER2) or CC49 (anti-TAG-72) were utilized as primary agents, and the small molecule HaloTag ligands 111In-HTL-1, -2, and -3 were evaluated as secondary agents. While this approach was not sufficiently sensitive to detect the internalizing HER2 antigen, pretargeting experiments involving the most optimal secondary agent, 111In-HTL-3, were successful in detecting the noninternalizing antigen TAG-72 and provided high-contrast SPECT images at 4 and 24 h postinjection.

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Citations

Dec 30, 2020·Cancers·Ruben D HouvastCornelis F M Sier
Mar 25, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Rachael Fay, Jason P Holland
Mar 24, 2020·Chemical Reviews·Weijun WeiWeibo Cai

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