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[F-18]-Fluoro-2-deoxy-d-glucose positron emission tomography as a tool for early detection of immunotherapy response in a murine B cell lymphoma model

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Abstract

[F-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is a non-invasive imaging technique which has recently been validated for the assessment of therapy response in patients with aggressive non-Hodgkin’s lymphoma. Our objective was to determine its value for the evaluation of immunotherapy efficacy in immunocompetent Balb/c mice injected with the A20 syngeneic B lymphoma cell line. The high level of in vitro FDG uptake by A20 cells validated the model for further imaging studies. When injected intravenously, the tumour developed as nodular lesions mostly in liver and spleen, thus mimicking the natural course of an aggressive human lymphoma. FDG-PET provided three-dimensionnal images of tumour extension including non-palpable lesions, in good correlation with ex vivo macroscopic examination. When mice were pre-immunized with an A20 cell lysate in adjuvant before tumour challenge, their significantly longer survival, compared to control mice, were associated with a lower incidence of lymphoma visualized by PET at different time points. Estimation of tumour growth and metabolism using the calculated tumour volumes and maximum standardized uptake values, respectively, also demonstrated delayed lymphoma development and lower activity in the vaccinated mice. Thus, FDG-PET is a sensitive tool relevant for early detection and follow-up of internal tumours, allowing discrimination between treated and non-treated small animal cohorts without invasive intervention.

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Acknowledgments

This work was supported by the French Association for Cancer Research (ARC grant no. 3257) and by ARTGIL (granted by Amgen and Roche France). C. Chaise was initially supported by a grant from the French ministry for education and research and subsequently from the Fondation pour la Recherche Médicale (FRM). We thank Gaël Grannec and Sandrine Machane for their help with animal care, Dr Fabrice Chrétien for photographs of the animals and Dr William Hempel for careful editing of the manuscript.

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Authors and Affiliations

  1. INSERM, U617, Créteil, 94000, France

    Coralie Chaise, Christiane Copie-Bergman, Jean-Pierre Farcet, Marie-Hélène Delfau-Larue & Valérie Molinier-Frenkel

  2. Faculté de Médecine, Université Paris 12, Créteil, 94000, France

    Coralie Chaise, Emmanuel Itti, Evelyne Wirquin, Christiane Copie-Bergman, Jean-Pierre Farcet, Marie-Hélène Delfau-Larue, Michel Meignan & Valérie Molinier-Frenkel

  3. Service de Médecine Nucléaire, AP-HP, Hôpital Henri Mondor, Créteil, 94000, France

    Emmanuel Itti, Evelyne Wirquin & Michel Meignan

  4. Service de Biophysique, AP-HP, Hôpital Tenon, Paris, France

    Yolande Petegnief & Jean-Noël Talbot

  5. Département de Pathologie, AP-HP, Hôpital Henri Mondor, Créteil, 94000, France

    Christiane Copie-Bergman

  6. Service d’Immunologie Biologique, AP-HP, Hôpital Henri Mondor, Créteil, 94000, France

    Jean-Pierre Farcet, Marie-Hélène Delfau-Larue & Valérie Molinier-Frenkel

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  1. Coralie Chaise
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  2. Emmanuel Itti
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  10. Valérie Molinier-Frenkel
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Correspondence to Valérie Molinier-Frenkel.

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C. Chaise and E. Itti contributed equally to the work.

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Chaise, C., Itti, E., Petegnief, Y. et al. [F-18]-Fluoro-2-deoxy-d-glucose positron emission tomography as a tool for early detection of immunotherapy response in a murine B cell lymphoma model. Cancer Immunol Immunother 56, 1163–1171 (2007). https://doi.org/10.1007/s00262-006-0265-0

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