Harnessing the bioorthogonal inverse electron demand Diels-Alder cycloaddition for pretargeted PET imaging Journal Article
| Authors: | Reiner, T.; Lewis, J. S.; Zeglis, B. M. |
| Article Title: | Harnessing the bioorthogonal inverse electron demand Diels-Alder cycloaddition for pretargeted PET imaging |
| Abstract: | Due to their exquisite affinity and specificity, antibodies have become extremely promising vectors for the delivery of radioisotopes to cancer cells for PET imaging. However, the necessity of labeling antibodies with radionuclides with long physical half-lives often results in high background radiation dose rates to non-target tissues. In order to circumvent this issue, we have employed a pretargeted PET imaging strategy based on the inverse electron demand Diels-Alder cycloaddition reaction. The methodology decouples the antibody from the radioactivity and thus exploits the positive characteristics of antibodies, while eschewing their pharmacokinetic drawbacks. The system is composed of four steps: (1) the injection of a mAb-trans-cyclooctene (TCO) conjugate; (2) a localization time period during which the antibody accumulates in the tumor and clears from the blood; (3) the injection of the radiolabeled tetrazine; and (4) the in vivo click ligation of the components followed by the clearance of excess radioligand. In the example presented in the work at hand, a64Cu-NOTA-labeled tetrazine radioligand and a trans-cyclooctene-conjugated humanized antibody (huA33) were successfully used to delineate SW1222 colorectal cancer tumors with high tumor-to-background contrast. Further, the pretargeting methodology produces high quality images at only a fraction of the radiation dose to non-target tissue created by radioimmunoconjugates directly labeled with64Cu or89Zr. Ultimately, the modularity of this protocol is one of its greatest assets, as the trans-cyclooctene moiety can be appended to any non-internalizing antibody, and the tetrazine can be attached to a wide variety of radioisotopes. © JoVE 2006-2015. All Rights Reserved. |
| Keywords: | positron emission tomography; click chemistry; bioengineering; pretargeting; tetrazine; inverse electron demand diels-alder cycloaddition; issue 96; trans-cyclooctene |
| Journal Title: | Journal of Visualized Experiments |
| Issue: | 96 |
| ISSN: | 1940-087X |
| Publisher: | MYJoVE Corporation |
| Date Published: | 2015-02-03 |
| Start Page: | e52335 |
| Language: | English |
| DOI: | 10.3791/52335 |
| PROVIDER: | scopus |
| PUBMED: | 25742199 |
| PMCID: | PMC4354619 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2015 -- Source: Scopus |
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