Single-Dose Anti-CD138 Radioimmunotherapy: Bismuth-213 is More Efficient than Lutetium-177 for Treatment of Multiple Myeloma in a Preclinical Model

单剂量抗 CD138 放射免疫疗法:在临床前模型中,铋-213 治疗多发性骨髓瘤比镥-177 更有效

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作者:Nolwenn Fichou, Sébastien Gouard, Catherine Maurel, Jacques Barbet, Ludovic Ferrer, Alfred Morgenstern, Frank Bruchertseifer, Alain Faivre-Chauvet, Edith Bigot-Corbel, François Davodeau, Joëlle Gaschet, Michel Chérel

Conclusion

This study revealed the advantages of α-RIT in the treatment of MM in a preclinical model where β-RIT shows almost no efficacy.

Methods

A new monoclonal anti-CD138 antibody, 9E7.4, was generated by immunizing a rat with a murine CD138-derived peptide. Antibody specificity was validated by flow cytometry, biodistribution, and α-RIT studies. Then, a β-RIT dose-escalation assay with the (177)Lu-radiolabeled 9E7.4 mAb was performed in KalwRij C57/BL6 mice 10 days after i.v. engraftment with 5T33 MM cells. Animal survival and toxicological parameters were assessed to define the optimal activity.

Results

α-RIT performed with 3.7 MBq of (213)Bi-labeled 9E7.4 anti-CD138 mAb increased median survival to 80 days compared to 37 days for the untreated control and effected cure in 45% of animals. β-RIT performed with 18.5 MBq of (177)Lu-labeled 9E7.4 mAb was well tolerated and significantly increased mouse survival (54 vs. 37 days in the control group); however, no mice were cured with this treatment.

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