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Preclinical Evaluation of Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis

Journal of Nuclear Medicine, ISSN: 2159-662X, Vol: 64, Issue: 4, Page: 555-560
2023
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Article 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 Zr-labeled bexmarilimab in rabbits. Methods: Bexmarilimab was conjugated with desferrioxamine (DFO) and radiolabeled with Zr. Retained immunoreactivity was confirmed by flow cytometry. The distribution kinetics of intravenously administered 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 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: 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 g-counting, and autoradiography demonstrated that there was significantly higher 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 Zr-DFO-bexmarili-mab support future human PET studies to, for example, stratify patients for bexmarilimab treatment, evaluate the efficacy of treatment, or monitor disease progression.

Bibliographic Details

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

Society of Nuclear Medicine

Medicine

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