Preclinical Evaluation of 89Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis

Olli Moisio, Jenni Virta, Emrah Yatkin, Heidi Liljenbäck, Senthil Palani, Riikka Viitanen, Maxwell W. G. Miner, Vesa Oikonen, Tuula Tolvanen, Danielle J. Vugts, Pekka Taimen, Xiang-Guo Li, Maija Hollmén, Sirpa Jalkanen, Anne Roivainen

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3 Citations (Scopus)

Abstract

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 89Zr-labeled bexmarilimab in rabbits. Methods: Bexmarilimab was conjugated with desferrioxamine (DFO) and radiolabeled with 89Zr. Retained immunoreactivity was confirmed by flow cytometry. The distribution kinetics of intravenously administered 89Zr-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 89Zr-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: 89Zr-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 89Zr-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 89Zr-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.
Original languageEnglish
Pages (from-to)555-560
Number of pages6
JournalJournal of nuclear medicine
Volume64
Issue number4
DOIs
Publication statusPublished - 1 Apr 2023

Keywords

  • CLEVER-1
  • PET/CT
  • Zr
  • bexmarilimab
  • renal fibrosis
  • whole-body distribution

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