PT  - JOURNAL ARTICLE
AU  - Moisio, Olli
AU  - Virta, Jenni
AU  - Yatkin, Emrah
AU  - Liljenbäck, Heidi
AU  - Palani, Senthil
AU  - Viitanen, Riikka
AU  - Miner, Maxwell W.G.
AU  - Oikonen, Vesa
AU  - Tolvanen, Tuula
AU  - Vugts, Danielle J.
AU  - Taimen, Pekka
AU  - Li, Xiang-Guo
AU  - Hollmén, Maija
AU  - Jalkanen, Sirpa
AU  - Roivainen, Anne
TI  - Preclinical Evaluation of <sup>89</sup>Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis
AID  - 10.2967/jnumed.122.264725
DP  - 2023 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 555--560
VI  - 64
IP  - 4
4099  - http://jnm.snmjournals.org/content/64/4/555.short
4100  - http://jnm.snmjournals.org/content/64/4/555.full
SO  - J Nucl Med2023 Apr 01; 64
AB  - 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 γ-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-bexmarilimab support future human PET studies to, for example, stratify patients for bexmarilimab treatment, evaluate the efficacy of treatment, or monitor disease progression.