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

• Published in: Molecular pharmaceutics Vol. 14; no. 7; pp. 2307 - 2313
• Main Authors: Knight, James C, Mosley, Michael, Uyeda, H. Tetsuo, Cong, Mei, Fan, Frank, Faulkner, Stephen, Cornelissen, Bart
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03.07.2017
• Subjects: Animals; Antigens, Neoplasm - metabolism; Cell Line, Tumor; Female; Glycoproteins - metabolism; Heterografts; Humans; Indium Radioisotopes - analysis; Mice; Radioimmunotherapy; Receptor, ErbB-2 - metabolism; Tomography, Emission-Computed, Single-Photon; delivery; HaloTag; pretargeting; molecular imaging; SPECT
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.7b00172

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.