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Early evaluation of the effects of chemotherapy with longitudinal FDG small-animal PET in human testicular cancer xenografts: early flare response does not reflect refractory disease

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Aim

We aimed to evaluate the usefulness of FDG PET in the early prediction of the effects of chemotherapy on human testicular cancer xenografts.

Material and methods

Nude rats bearing subcutaneous human embryonal carcinoma xenografts received either cisplatin (5 mg/kg) or saline serum. Small-animal PET studies were performed on days 0, 2, 4 and 7 and compared to immunochemistry studies, flow cytometry studies and hexokinase assays.

Results

Cisplatin treatment resulted in biphasic FDG uptake evolution: a peak was observed on day 2, followed by a marked decrease on day 7 despite an insignificant change in tumour volume. Similarly, a peak in cyclin A immunostaining was observed on days 2 and 4), followed by a significant decrease on day 7. Flow cytometry showed that the cyclin A peak was not related to increased cell proliferation but was due to a transient S and G2/M cell cycle arrest. A marked increase in cell apoptosis was observed from day 2 to day 7. GLUT-1 showed a significant decrease on day 7. Macrophagic infiltrate remained stable except for an increase observed on day 7. In control tumours, continuous growth was observed, all immunostaining markers remaining stable over time. Hexokinase activity was significantly lower on day 7 in treated tumours than in controls.

Conclusion

FDG PET may be useful in the early evaluation of treatment in patients with testicular cancer. In our model, a very early increased [18F]-FDG uptake was related to a transient cell cycle arrest and early stage apoptosis but did not reveal refractory disease.

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Acknowledgments

This work was supported by a grant from the French Ligue Contre le Cancer, Comité du Calvados. Alexandre Labiche received a fellowship from the Ligue Contre le Cancer, Comité de la Manche. The authors wish to thank Dr. Jacques Chasles (Pathology Department, François Baclesse Centre) for GLUT-1 immunochemistry study analysis, Edwige Lemoisson (Biotical Unit, GRECAN) for cell line management, and Dr. Charbel Mehreb for SA-PET calibrations. The authors also thank Dr. Gutman for his critical review of the manuscript.

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Authors and Affiliations

  1. Bioticla Unit, GRECAN, EA 1772, IFR 146 ICORE, Caen University, Caen, France

    Nicolas Aide, Laurent Poulain, Mélanie Briand, Soizic Dutoit, Alexandre Labiche & Pascal Gauduchon

  2. Nuclear Medicine Department, François Baclesse Comprehensive Cancer Centre, Caen, France

    Nicolas Aide

  3. Biochemistry Department, University Hospital, Caen, France

    Stéphane Allouche

  4. LIMP, Tenon Hospital and University Pierre et Marie Curie (Paris 6), Paris, France

    Aurélie Ngo-Van Do, Valérie Nataf, Jean-noël Talbot & Françoise Montravers

  5. Medical Physics Unit, François Baclesse Comprehensive Cancer Centre, Caen, France

    Alain Batalla

  6. Service de Médecine Nucléaire, Centre François Baclesse, Avenue Général Harris, 14076, Caen Cedex 5, France

    Nicolas Aide

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  1. Nicolas Aide
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Correspondence to Nicolas Aide.

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Aide, N., Poulain, L., Briand, M. et al. Early evaluation of the effects of chemotherapy with longitudinal FDG small-animal PET in human testicular cancer xenografts: early flare response does not reflect refractory disease. Eur J Nucl Med Mol Imaging 36, 396–405 (2009). https://doi.org/10.1007/s00259-008-0984-x

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  • DOI: https://doi.org/10.1007/s00259-008-0984-x

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