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Translational Therapeutics

Preclinical study of 212Pb alpha-radioimmunotherapy targeting CD20 in non-Hodgkin lymphoma

British Journal of Cancer volume 125, pages 1657–1665 (2021)Cite this article

Subjects

Abstract

Background

Despite therapeutic advances, Non-Hodgkin lymphoma (NHL) relapses can occur. The development of radioimmunotherapy (RIT) with α-emitters is an attractive alternative. In this study, we investigated the potential of α-RIT in conjunction with 212Pb-rituximab for the treatment of NHL.

Methods

EL4-hCD20-Luc cells (mouse lymphoma cell line) were used for in vitro and in vivo studies. Biodistribution and efficacy studies were performed on C57BL/6 mice injected intravenously with 25 × 103 cells.

Results

212Pb-rituximab (0.925–7.4 kBq/mL) inhibit proliferation of EL4-hCD20-Luc cells in vitro. Biodistribution of 203/212Pb-rituximab in mice showed a significant tumour uptake and suggested that the liver, spleen, and kidneys were the organs at risk. For efficacy studies, mice were treated at either 11 days (early stage) or 20–30 days after injection of tumour cells (late stage). Treatment with 277.5 kBq 212Pb-rituximab significantly prolonged survival. Even at an advanced tumour stage, significant tumour regression occurred, with an increase in the median survival time to 28 days, compared with 9 days in the controls.

Conclusions

These results show the efficacy of 212Pb-rituximab in a murine syngeneic lymphoma model, in terms of significant tumour regression and increased survival, thereby highlighting the potency of α-RIT for the treatment of NHL.

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Fig. 1: In vitro studies.
Fig. 2: Biodistribution and SPECT-CT imaging.
Fig. 3: Toxicity studies.
Fig. 4: Efficacy of 212Pb-rituximab treatment in a murine syngeneic lymphoma model at an early stage.
Fig. 5: Efficacy of 212Pb-rituximab treatment in a late-stage murine syngeneic lymphoma model.
Fig. 6: BLI monitoring in a late-stage murine syngeneic lymphoma model.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

CRIBL is member of the Consortium for the Acceleration of Innovation and its Transfer in the Lymphoma Field (CALYM) Carnot Institute www.calym.org. We would also like to thank Dr. Jeanne Cook-Moreau for proofreading and our radiation protection officer, Dr. Eric Pinaud.

Funding

This research was supported by BPI France.

Author information

Authors and Affiliations

  1. CNRS-UMR7276 – INSERM U1262, Contrôle de la réponse immune B et lymphoproliférations, Limoges University, Limoges, France

    Stéphanie Durand-Panteix, Jacques Monteil, Magali Sage, Marie Clavel, Michel Cogne & Isabelle Quelven

  2. Nuclear Medicine Department, Limoges University Hospital, Limoges, France

    Jacques Monteil, Armand Garot & Isabelle Quelven

  3. Orano Med SAS, Paris, France

    Amal Saidi & Julien Torgue

  4. ToNIC, Toulouse NeuroImaging Center - INSERM U1214, Toulouse, France

    Isabelle Quelven

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  1. Stéphanie Durand-Panteix
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Contributions

SDP, JM, AS, JT, MiC and IQ conceptualised the study; SDP and IQ assembled, analysed and interpreted data, and wrote the manuscript; MS, AG and MaC performed experiments and collected the data; JM and IQ performed SPECT/CT imaging treatment; AS, JT and MiC helped with manuscript preparation.

Corresponding authors

Correspondence to Michel Cogne or Isabelle Quelven.

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Competing interests

Amal Saidi and Julien Torgue are Orano Med employees. No other potential conflicts of interest relevant to this article exist.

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All applicable international, national and institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Durand-Panteix, S., Monteil, J., Sage, M. et al. Preclinical study of 212Pb alpha-radioimmunotherapy targeting CD20 in non-Hodgkin lymphoma. Br J Cancer 125, 1657–1665 (2021). https://doi.org/10.1038/s41416-021-01585-6

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