Inverse electron demand Diels–Alder click chemistry for pretargeted PET imaging and radioimmunotherapy Journal Article


Authors: Sarrett, S. M.; Keinänen, O.; Dayts, E. J.; Dewaele-Le Roi, G.; Rodriguez, C.; Carnazza, K. E.; Zeglis, B. M.
Article Title: Inverse electron demand Diels–Alder click chemistry for pretargeted PET imaging and radioimmunotherapy
Abstract: Radiolabeled antibodies have shown promise as tools for both the nuclear imaging and endoradiotherapy of cancer, but the protracted circulation time of radioimmunoconjugates can lead to high radiation doses to healthy tissues. To circumvent this issue, we have developed an approach to positron emission tomography (PET) imaging and radioimmunotherapy (RIT) predicated on radiolabeling the antibody after it has reached its target within the body. This in vivo pretargeting strategy is based on the rapid and bio-orthogonal inverse electron demand Diels–Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO). Pretargeted PET imaging and RIT using TCO-modified antibodies in conjunction with Tz-bearing radioligands produce high activity concentrations in target tissues as well as reduced radiation doses to healthy organs compared to directly labeled radioimmunoconjugates. Herein, we describe how to prepare a TCO-modified antibody (humanized A33-TCO) as well as how to synthesize two Tz-bearing radioligands: one labeled with the positron-emitting radiometal copper-64 ([64Cu]Cu-SarAr-Tz) and one labeled with the β-emitting radiolanthanide lutetium-177 ([177Lu]Lu-DOTA-PEG7-Tz). We also provide a detailed description of pretargeted PET and pretargeted RIT experiments in a murine model of human colorectal carcinoma. Proper training in both radiation safety and the handling of laboratory mice is required for the successful execution of this protocol. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Journal Title: Nature Protocols
Volume: 16
Issue: 7
ISSN: 1754-2189
Publisher: Nature Publishing Group  
Date Published: 2021-07-01
Start Page: 3348
End Page: 3381
Language: English
DOI: 10.1038/s41596-021-00540-2
PUBMED: 34127865
PROVIDER: scopus
PMCID: PMC8917728
DOI/URL:
Notes: Review -- Export Date: 2 August 2021 -- Source: Scopus
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  1. Brian Zeglis
    88 Zeglis