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Multimodal imaging based on MRI and PET reveals [18F]FLT PET as a specific and early indicator of treatment efficacy in a preclinical model of recurrent glioblastoma

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Abstract

Purpose

The primary objective of this study was to compare the ability of PET and MRI biomarkers to predict treatment efficacy in a preclinical model of recurrent glioblastoma multiforme.

Methods

MRI (anatomical, diffusion, vasculature and oxygenation) and PET ([18F]FDG and [18F]FLT) parameters were obtained 3 days after the end of treatment and compared with late tumour growth and survival.

Results

Early after tumour recurrence, no effect of treatment with temozolomide combined with bevacizumab was observed on tumour volume as assessed by T2-W MRI. At later times, the treatment decreased tumour volume and increased survival. Interestingly, at the earlier time, temozolomide + bevacizumab decreased [18F]FLT uptake, cerebral blood volume and oedema. [18F]FLT uptake, oedema and cerebral blood volume were correlated with overall survival but [18F]FLT uptake had the highest specificity and sensitivity for the early prediction of treatment efficacy.

Conclusion

The present investigation in a preclinical model of glioblastoma recurrence underscores the importance of multimodal imaging in the assessment of oedema, tumour vascular status and cell proliferation. Finally, [18F]FLT holds the greatest promise for the early assessment of treatment efficacy. These findings may translate clinically in that individualized treatment for recurrent glioma could be prescribed for patients selected after PET/MRI examinations.

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Authors and Affiliations

  1. CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France

    Aurélien Corroyer-Dulmont, Elodie A. Pérès, Aurélie N. Gérault, Didier Divoux, Jérôme Toutain, Méziane Ibazizène, Eric T. MacKenzie, Louisa Barré, Myriam Bernaudin, Edwige Petit & Samuel Valable

  2. CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France

    Aurélien Corroyer-Dulmont, Elodie A. Pérès, Aurélie N. Gérault, Didier Divoux, Jérôme Toutain, Méziane Ibazizène, Eric T. MacKenzie, Louisa Barré, Myriam Bernaudin, Edwige Petit & Samuel Valable

  3. UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France

    Aurélien Corroyer-Dulmont, Elodie A. Pérès, Aurélie N. Gérault, Didier Divoux, Jérôme Toutain, Méziane Ibazizène, Eric T. MacKenzie, Louisa Barré, Myriam Bernaudin, Edwige Petit & Samuel Valable

  4. Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France

    Aurélien Corroyer-Dulmont, Elodie A. Pérès, Aurélie N. Gérault, Didier Divoux, Jérôme Toutain, Méziane Ibazizène, Eric T. MacKenzie, Louisa Barré, Myriam Bernaudin, Edwige Petit & Samuel Valable

  5. Roche SAS, 30, cours de l’Ile Seguin, 92650, Boulogne-Billancourt, France

    Ariel Savina & Fanny Bouquet

Authors
  1. Aurélien Corroyer-Dulmont
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  2. Elodie A. Pérès
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  3. Aurélie N. Gérault
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  13. Samuel Valable
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Corresponding author

Correspondence to Samuel Valable.

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Funding

This study was funded by the Institut National contre le Cancer (INCa), Roche, the Centre National de la Recherche Scientifique (CNRS), the French Ministère de l′Enseignement Supérieur et de la Recherche (MESR) and the University of Caen-Basse Normandie (UCBN), the Conseil Régional de Basse-Normandie, the European Union-Fonds Européen de Développement Régional (FEDER), the French Agence Nationale de la Recherche (ANR-11-LABX-18-01 “Investissements d’Avenir” and ANR-2011-BSV5-004-03) and the Trans Channel Neuroscience Network (TC2N).

Conflicts of interest

Ariel Savina and Fanny Bouquet are employed by Roche.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted as detailed in the “Materials and methods” section.

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Corroyer-Dulmont, A., Pérès, E.A., Gérault, A.N. et al. Multimodal imaging based on MRI and PET reveals [18F]FLT PET as a specific and early indicator of treatment efficacy in a preclinical model of recurrent glioblastoma. Eur J Nucl Med Mol Imaging 43, 682–694 (2016). https://doi.org/10.1007/s00259-015-3225-0

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  • DOI: https://doi.org/10.1007/s00259-015-3225-0

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