Lookup NU author(s): Dr James Knight
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 American Chemical Society. 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.
Author(s): Knight JC, Mosley M, Uyeda HT, Cong M, Fan F, Faulkner S, Cornelissen B
Publication type: Article
Publication status: Published
Journal: Molecular Pharmaceutics
Print publication date: 03/07/2017
Online publication date: 15/05/2017
Acceptance date: 15/05/2017
Date deposited: 30/08/2018
ISSN (print): 1543-8384
ISSN (electronic): 1543-8392
Publisher: American Chemical Society
PubMed id: 28505463
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