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Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [(89)Zr]Zr-DFO-PEG(5)-Tz
[Image: see text] The recent advances in the production of engineered antibodies have facilitated the development and application of tailored, target-specific antibodies. Positron emission tomography (PET) of these antibody-based drug candidates can help to better understand their in vivo behavior....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121349/ https://www.ncbi.nlm.nih.gov/pubmed/35442642 http://dx.doi.org/10.1021/acs.bioconjchem.2c00164 |
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author | Lumen, Dave Vugts, Danielle Chomet, Marion Imlimthan, Surachet Sarparanta, Mirkka Vos, Ricardo Schreurs, Maxime Verlaan, Mariska Lang, Pauline A. Hippeläinen, Eero Beaino, Wissam Windhorst, Albert D. Airaksinen, Anu J. |
author_facet | Lumen, Dave Vugts, Danielle Chomet, Marion Imlimthan, Surachet Sarparanta, Mirkka Vos, Ricardo Schreurs, Maxime Verlaan, Mariska Lang, Pauline A. Hippeläinen, Eero Beaino, Wissam Windhorst, Albert D. Airaksinen, Anu J. |
author_sort | Lumen, Dave |
collection | PubMed |
description | [Image: see text] The recent advances in the production of engineered antibodies have facilitated the development and application of tailored, target-specific antibodies. Positron emission tomography (PET) of these antibody-based drug candidates can help to better understand their in vivo behavior. In this study, we report an in vivo proof-of-concept pretargeted immuno-PET study where we compare a pretargeting vs targeted approach using a new (89)Zr-labeled tetrazine as a bio-orthogonal ligand in an inverse electron demand Diels–Alder (IEDDA) in vivo click reaction. A CD44v6-selective chimeric monoclonal U36 was selected as the targeting antibody because it has potential in immuno-PET imaging of head-and-neck squamous cell carcinoma (HNSCC). Zirconium-89 (t(1/2) = 78.41 h) was selected as the radionuclide of choice to be able to make a head-to-head comparison of the pretargeted and targeted approaches. [(89)Zr]Zr-DFO-PEG(5)-Tz ([(89)Zr]Zr-3) was synthesized and used in pretargeted PET imaging of HNSCC xenografts (VU-SCC-OE) at 24 and 48 h after administration of a trans-cyclooctene (TCO)-functionalized U36. The pretargeted approach resulted in lower absolute tumor uptake than the targeted approach (1.5 ± 0.2 vs 17.1 ± 3.0% ID/g at 72 h p.i. U36) but with comparable tumor-to-non-target tissue ratios and significantly lower absorbed doses. In conclusion, anti-CD44v6 monoclonal antibody U36 was successfully used for (89)Zr-immuno-PET imaging of HNSCC xenograft tumors using both a targeted and pretargeted approach. The results not only support the utility of the pretargeted approach in immuno-PET imaging but also demonstrate the challenges in achieving optimal in vivo IEDDA reaction efficiencies in relation to antibody pharmacokinetics. |
format | Online Article Text |
id | pubmed-9121349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-91213492022-05-21 Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [(89)Zr]Zr-DFO-PEG(5)-Tz Lumen, Dave Vugts, Danielle Chomet, Marion Imlimthan, Surachet Sarparanta, Mirkka Vos, Ricardo Schreurs, Maxime Verlaan, Mariska Lang, Pauline A. Hippeläinen, Eero Beaino, Wissam Windhorst, Albert D. Airaksinen, Anu J. Bioconjug Chem [Image: see text] The recent advances in the production of engineered antibodies have facilitated the development and application of tailored, target-specific antibodies. Positron emission tomography (PET) of these antibody-based drug candidates can help to better understand their in vivo behavior. In this study, we report an in vivo proof-of-concept pretargeted immuno-PET study where we compare a pretargeting vs targeted approach using a new (89)Zr-labeled tetrazine as a bio-orthogonal ligand in an inverse electron demand Diels–Alder (IEDDA) in vivo click reaction. A CD44v6-selective chimeric monoclonal U36 was selected as the targeting antibody because it has potential in immuno-PET imaging of head-and-neck squamous cell carcinoma (HNSCC). Zirconium-89 (t(1/2) = 78.41 h) was selected as the radionuclide of choice to be able to make a head-to-head comparison of the pretargeted and targeted approaches. [(89)Zr]Zr-DFO-PEG(5)-Tz ([(89)Zr]Zr-3) was synthesized and used in pretargeted PET imaging of HNSCC xenografts (VU-SCC-OE) at 24 and 48 h after administration of a trans-cyclooctene (TCO)-functionalized U36. The pretargeted approach resulted in lower absolute tumor uptake than the targeted approach (1.5 ± 0.2 vs 17.1 ± 3.0% ID/g at 72 h p.i. U36) but with comparable tumor-to-non-target tissue ratios and significantly lower absorbed doses. In conclusion, anti-CD44v6 monoclonal antibody U36 was successfully used for (89)Zr-immuno-PET imaging of HNSCC xenograft tumors using both a targeted and pretargeted approach. The results not only support the utility of the pretargeted approach in immuno-PET imaging but also demonstrate the challenges in achieving optimal in vivo IEDDA reaction efficiencies in relation to antibody pharmacokinetics. American Chemical Society 2022-04-20 2022-05-18 /pmc/articles/PMC9121349/ /pubmed/35442642 http://dx.doi.org/10.1021/acs.bioconjchem.2c00164 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Lumen, Dave Vugts, Danielle Chomet, Marion Imlimthan, Surachet Sarparanta, Mirkka Vos, Ricardo Schreurs, Maxime Verlaan, Mariska Lang, Pauline A. Hippeläinen, Eero Beaino, Wissam Windhorst, Albert D. Airaksinen, Anu J. Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [(89)Zr]Zr-DFO-PEG(5)-Tz |
title | Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6
Chimeric mAb U36 and [(89)Zr]Zr-DFO-PEG(5)-Tz |
title_full | Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6
Chimeric mAb U36 and [(89)Zr]Zr-DFO-PEG(5)-Tz |
title_fullStr | Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6
Chimeric mAb U36 and [(89)Zr]Zr-DFO-PEG(5)-Tz |
title_full_unstemmed | Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6
Chimeric mAb U36 and [(89)Zr]Zr-DFO-PEG(5)-Tz |
title_short | Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6
Chimeric mAb U36 and [(89)Zr]Zr-DFO-PEG(5)-Tz |
title_sort | pretargeted pet imaging with a tco-conjugated anti-cd44v6
chimeric mab u36 and [(89)zr]zr-dfo-peg(5)-tz |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121349/ https://www.ncbi.nlm.nih.gov/pubmed/35442642 http://dx.doi.org/10.1021/acs.bioconjchem.2c00164 |
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