RT Journal Article
SR Electronic
T1 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
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 555
OP 560
DO 10.2967/jnumed.122.264725
VO 64
IS 4
A1 Moisio, Olli
A1 Virta, Jenni
A1 Yatkin, Emrah
A1 Liljenbäck, Heidi
A1 Palani, Senthil
A1 Viitanen, Riikka
A1 Miner, Maxwell W.G.
A1 Oikonen, Vesa
A1 Tolvanen, Tuula
A1 Vugts, Danielle J.
A1 Taimen, Pekka
A1 Li, Xiang-Guo
A1 Hollmén, Maija
A1 Jalkanen, Sirpa
A1 Roivainen, Anne
YR 2023
UL http://jnm.snmjournals.org/content/64/4/555.abstract
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.