A1 Refereed original research article in a scientific journal
Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [Zr-89]Zr-DFO-PEG(5)-Tz
Authors: 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
Publisher: AMER CHEMICAL SOC
Publication year: 2022
Journal: Bioconjugate Chemistry
Journal name in source: BIOCONJUGATE CHEMISTRY
Journal acronym: BIOCONJUGATE CHEM
Volume: 33
Issue: 5
First page : 956
Last page: 968
Number of pages: 13
ISSN: 1043-1802
eISSN: 1520-4812
DOI: https://doi.org/10.1021/acs.bioconjchem.2c00164
Web address : https://pubs.acs.org/doi/10.1021/acs.bioconjchem.2c00164
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/175399335
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-ofconcept pretargeted immuno-PET study where we compare a pretargeting vs targeted approach using a new Zr-89-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. [Zr-89]Zr-DFO-PEG S -Tz ([Zr-89]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 Zr-89-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.
Downloadable publication This is an electronic reprint of the original article. |  |
