James C Knight, Michael Mosley, H Tetsuo Uyeda, Mei Cong, Frank Fan, Stephen Faulkner, Bart Cornelissen
Molecular pharmaceutics 2017 Jul 03A 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.
James C Knight, Michael Mosley, H Tetsuo Uyeda, Mei Cong, Frank Fan, Stephen Faulkner, Bart Cornelissen. In Vivo Pretargeted Imaging of HER2 and TAG-72 Expression Using the HaloTag Enzyme. Molecular pharmaceutics. 2017 Jul 03;14(7):2307-2313
PMID: 28505463
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