Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)

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




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

KustantajaSociety of Nuclear Medicine

Julkaisuvuosi2022

JournalJournal of Nuclear Medicine

Tietokannassa oleva lehden nimiJournal of nuclear medicine : official publication, Society of Nuclear Medicine

Lehden akronyymiJ Nucl Med

ISSN0161-5505

eISSN1535-5667

DOIhttp://dx.doi.org/10.2967/jnumed.122.264725

Verkko-osoitehttps://doi.org/10.2967/jnumed.122.264725

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/177850854


Tiivistelmä

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 to 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. Distribution kinetics of intravenously administered 89Zr-DFO-bexmarilimab (0.1 mg/kg) for up to 7 days in a rabbit model of renal fibrosis mediated by unilateral ureteric obstruction (UUO). 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 hours post-injection, PET/CT, ex-vivo gamma counting and autoradiography demonstrated that there was significantly higher 89Zr-DFO-bexmarilimab uptake in UUO-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.


Ladattava julkaisu

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.




Last updated on 2023-18-04 at 14:01