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Preclinical Evaluation of (89)Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis
Bexmarilimab is a new humanized monoclonal antibody against common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) and is in clinical trials for macrophage-guided cancer immunotherapy. In addition being associated with cancer, CLEVER-1 is also associated with fibrosis. To facili...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society of Nuclear Medicine
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071790/ https://www.ncbi.nlm.nih.gov/pubmed/36302655 http://dx.doi.org/10.2967/jnumed.122.264725 |
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author | Moisio, Olli Virta, Jenni Yatkin, Emrah Liljenbäck, Heidi Palani, Senthil Viitanen, Riikka Miner, Maxwell W.G. Oikonen, Vesa Tolvanen, Tuula Vugts, Danielle J. Taimen, Pekka Li, Xiang-Guo Hollmén, Maija Jalkanen, Sirpa Roivainen, Anne |
author_facet | Moisio, Olli Virta, Jenni Yatkin, Emrah Liljenbäck, Heidi Palani, Senthil Viitanen, Riikka Miner, Maxwell W.G. Oikonen, Vesa Tolvanen, Tuula Vugts, Danielle J. Taimen, Pekka Li, Xiang-Guo Hollmén, Maija Jalkanen, Sirpa Roivainen, Anne |
author_sort | Moisio, Olli |
collection | PubMed |
description | Bexmarilimab is a new humanized monoclonal antibody against common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) and is in clinical trials for macrophage-guided cancer immunotherapy. In addition being associated with cancer, CLEVER-1 is also associated with fibrosis. To facilitate prospective human PET studies, we preclinically evaluated (89)Zr-labeled bexmarilimab in rabbits. Methods: Bexmarilimab was conjugated with desferrioxamine (DFO) and radiolabeled with (89)Zr. Retained immunoreactivity was confirmed by flow cytometry. The distribution kinetics of intravenously administered (89)Zr-DFO-bexmarilimab (0.1 mg/kg) were determined for up to 7 d in a rabbit model of renal fibrosis mediated by unilateral ureteric obstruction. The in vivo stability of (89)Zr-DFO-bexmarilimab was evaluated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis in combination with autoradiography. Additionally, we estimated the human radiation dose from data obtained in healthy rabbits. Results: (89)Zr-DFO-bexmarilimab cleared rapidly from the blood circulation and distributed to the liver and spleen. At 24 h after injection, PET/CT, ex vivo γ-counting, and autoradiography demonstrated that there was significantly higher (89)Zr-DFO-bexmarilimab uptake in unilateral ureteric obstruction–operated fibrotic renal cortex, characterized by abundant CLEVER-1–positive cells, than in contralateral or healthy kidneys. The estimated effective dose for a 70-kg human was 0.70 mSv/MBq. Conclusion: The characteristics of (89)Zr-DFO-bexmarilimab support future human PET studies to, for example, stratify patients for bexmarilimab treatment, evaluate the efficacy of treatment, or monitor disease progression. |
format | Online Article Text |
id | pubmed-10071790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Society of Nuclear Medicine |
record_format | MEDLINE/PubMed |
spelling | pubmed-100717902023-04-19 Preclinical Evaluation of (89)Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis Moisio, Olli Virta, Jenni Yatkin, Emrah Liljenbäck, Heidi Palani, Senthil Viitanen, Riikka Miner, Maxwell W.G. Oikonen, Vesa Tolvanen, Tuula Vugts, Danielle J. Taimen, Pekka Li, Xiang-Guo Hollmén, Maija Jalkanen, Sirpa Roivainen, Anne J Nucl Med Basic Science Investigation Bexmarilimab is a new humanized monoclonal antibody against common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) and is in clinical trials for macrophage-guided cancer immunotherapy. In addition being associated with cancer, CLEVER-1 is also associated with fibrosis. To facilitate prospective human PET studies, we preclinically evaluated (89)Zr-labeled bexmarilimab in rabbits. Methods: Bexmarilimab was conjugated with desferrioxamine (DFO) and radiolabeled with (89)Zr. Retained immunoreactivity was confirmed by flow cytometry. The distribution kinetics of intravenously administered (89)Zr-DFO-bexmarilimab (0.1 mg/kg) were determined for up to 7 d in a rabbit model of renal fibrosis mediated by unilateral ureteric obstruction. The in vivo stability of (89)Zr-DFO-bexmarilimab was evaluated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis in combination with autoradiography. Additionally, we estimated the human radiation dose from data obtained in healthy rabbits. Results: (89)Zr-DFO-bexmarilimab cleared rapidly from the blood circulation and distributed to the liver and spleen. At 24 h after injection, PET/CT, ex vivo γ-counting, and autoradiography demonstrated that there was significantly higher (89)Zr-DFO-bexmarilimab uptake in unilateral ureteric obstruction–operated fibrotic renal cortex, characterized by abundant CLEVER-1–positive cells, than in contralateral or healthy kidneys. The estimated effective dose for a 70-kg human was 0.70 mSv/MBq. Conclusion: The characteristics of (89)Zr-DFO-bexmarilimab support future human PET studies to, for example, stratify patients for bexmarilimab treatment, evaluate the efficacy of treatment, or monitor disease progression. Society of Nuclear Medicine 2023-04 /pmc/articles/PMC10071790/ /pubmed/36302655 http://dx.doi.org/10.2967/jnumed.122.264725 Text en © 2023 by the Society of Nuclear Medicine and Molecular Imaging. https://creativecommons.org/licenses/by/4.0/Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: http://jnm.snmjournals.org/site/misc/permission.xhtml. |
spellingShingle | Basic Science Investigation Moisio, Olli Virta, Jenni Yatkin, Emrah Liljenbäck, Heidi Palani, Senthil Viitanen, Riikka Miner, Maxwell W.G. Oikonen, Vesa Tolvanen, Tuula Vugts, Danielle J. Taimen, Pekka Li, Xiang-Guo Hollmén, Maija Jalkanen, Sirpa Roivainen, Anne Preclinical Evaluation of (89)Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis |
title | Preclinical Evaluation of (89)Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis |
title_full | Preclinical Evaluation of (89)Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis |
title_fullStr | Preclinical Evaluation of (89)Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis |
title_full_unstemmed | Preclinical Evaluation of (89)Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis |
title_short | Preclinical Evaluation of (89)Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis |
title_sort | preclinical evaluation of (89)zr-desferrioxamine-bexmarilimab, a humanized antibody against common lymphatic endothelial and vascular endothelial receptor-1, in a rabbit model of renal fibrosis |
topic | Basic Science Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071790/ https://www.ncbi.nlm.nih.gov/pubmed/36302655 http://dx.doi.org/10.2967/jnumed.122.264725 |
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