In vivo pretargeted imaging of HER2 and TAG-72 expression using the HaloTag enzyme
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 non-internal...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
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American Chemical Society
2017
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| _version_ | 1797084289598226432 |
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| author | Knight, J Mosley, M Uyeda, T Cong, M Fan, F Faulkner, S Cornelissen, B |
| author_facet | Knight, J Mosley, M Uyeda, T Cong, M Fan, F Faulkner, S Cornelissen, B |
| author_sort | Knight, J |
| collection | OXFORD |
| description | 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 non-internalizing 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 non-internalizing antigen TAG-72 and provided high contrast SPECT images at 4 and 24 h post-injection. |
| first_indexed | 2024-03-07T01:53:23Z |
| format | Journal article |
| id | oxford-uuid:9ae6d9f2-c2e1-4218-8e60-301c76a84b32 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:53:23Z |
| publishDate | 2017 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:9ae6d9f2-c2e1-4218-8e60-301c76a84b322022-03-27T00:24:34ZIn vivo pretargeted imaging of HER2 and TAG-72 expression using the HaloTag enzymeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9ae6d9f2-c2e1-4218-8e60-301c76a84b32Symplectic Elements at OxfordAmerican Chemical Society2017Knight, JMosley, MUyeda, TCong, MFan, FFaulkner, SCornelissen, BA 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 non-internalizing 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 non-internalizing antigen TAG-72 and provided high contrast SPECT images at 4 and 24 h post-injection. |
| spellingShingle | Knight, J Mosley, M Uyeda, T Cong, M Fan, F Faulkner, S Cornelissen, B In vivo pretargeted imaging of HER2 and TAG-72 expression using the HaloTag enzyme |
| title | In vivo pretargeted imaging of HER2 and TAG-72 expression using the HaloTag enzyme |
| title_full | In vivo pretargeted imaging of HER2 and TAG-72 expression using the HaloTag enzyme |
| title_fullStr | In vivo pretargeted imaging of HER2 and TAG-72 expression using the HaloTag enzyme |
| title_full_unstemmed | In vivo pretargeted imaging of HER2 and TAG-72 expression using the HaloTag enzyme |
| title_short | In vivo pretargeted imaging of HER2 and TAG-72 expression using the HaloTag enzyme |
| title_sort | in vivo pretargeted imaging of her2 and tag 72 expression using the halotag enzyme |
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