Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [89Zr]Zr-DFO-PEG5-Tz
| العنوان: | Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [89Zr]Zr-DFO-PEG5-Tz |
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| المؤلفون: | Dave Lumen, Danielle Vugts, Marion Chomet, Surachet Imlimthan, Mirkka Sarparanta, Ricardo Vos, Maxime Schreurs, Mariska Verlaan, Pauline A. Lang, Eero Hippeläinen, Wissam Beaino, Albert D. Windhorst, Anu J. Airaksinen |
| المساهمون: | Radiology and nuclear medicine, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Brain Imaging, Department of Chemistry, Tracers in Molecular Imaging (TRIM), HUS Medical Imaging Center, HUS Diagnostic Center, Department of Diagnostics and Therapeutics |
| المصدر: | Lumen, D, Vugts, D, Chomet, M, Imlimthan, S, Sarparanta, M, Vos, R, Schreurs, M, Verlaan, M, Lang, P A, Hippeläinen, E, Beaino, W, Windhorst, A D & Airaksinen, A J 2022, ' Pretargeted PET Imaging with a TCO-Conjugated Anti-CD44v6 Chimeric mAb U36 and [89Zr]Zr-DFO-PEG5-Tz ', Bioconjugate chemistry, vol. 33, no. 5, pp. 956-968 . https://doi.org/10.1021/acs.bioconjchem.2c00164 Bioconjugate chemistry, 33(5), 956-968. American Chemical Society |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Pharmacology, IN-VIVO CHEMISTRY, Organic Chemistry, ANTIGEN, 116 Chemical sciences, Biomedical Engineering, Pharmaceutical Science, CD44V6, Bioengineering, RADIOIMMUNOTHERAPY, MONOCLONAL-ANTIBODY U36, POSITRON-EMISSION-TOMOGRAPHY, CLICK CHEMISTRY, 1182 Biochemistry, cell and molecular biology, SQUAMOUS-CELL CARCINOMA, HEAD, Biotechnology, IMMUNO-PET |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.2c00164 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9303fabee94f0e86e8d38f0c62156b58 https://research.vumc.nl/en/publications/fb160ada-3f47-43a5-8d49-1816af8ce10b |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9303fabee94f0e86e8d38f0c62156b58 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10431802 |
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| DOI: | 10.1021/acs.bioconjchem.2c00164 |