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[18F]FDG PET monitoring of tumour response to chemotherapy: does [18F]FDG uptake correlate with the viable tumour cell fraction?

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Abstract

Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) is thought to predict response to therapy earlier and more accurately than other modalities. To be a reliable predictor of response, changes in tumour [18F]FDG uptake should reflect changes in viable cell fraction, but little is known about the contribution of apoptotic and necrotic cancer cells and inflammatory tissue to the [18F]FDG signal. In a tumour mouse model we investigated the relation between chemotherapy-induced changes in various tumoral components and tumour uptake and size. SCID mice were subcutaneously inoculated in the right thigh with 5×106 Daudi cells. When the tumour measured 15–20 mm, Endoxan was given intravenously. At different time points [1–15 days (d1–d15) after the injection of Endoxan], ex vivo autoradiography and histopathology were performed in two mice and [18F]FDG uptake in the tumour and tumour size were correlated with the different cell fractions measured with flow cytometry in five mice. At d1/d3, similar reductions in [18F]FDG uptake and viable tumoral cell fraction were observed and these reductions preceded changes in tumour size. By d8/d10, [18F]FDG uptake had stabilised despite a further reduction in viable tumoral cell fraction. At these time points a major inflammatory response was observed. At d15, an increase in viable tumour cells was again observed and this was accurately predicted by an increase in [18F]FDG uptake, while the tumour volume remained unchanged. In contrast with variations in tumour volume, [18F]FDG is a good marker for chemotherapy response monitoring. However, optimal timing seems crucial since a transient increase in stromal reaction may result in overestimation of the fraction of viable cells.

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Acknowledgements

We thank Peter Vermaelen and Werner Scheers for their technical support.

This study was supported by grant G.0298.97 from FWO-Vlaanderen (Fonds voor Wetenschappelijk Onderzoek Vlaanderen).

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Authors and Affiliations

  1. Department of Nuclear Medicine, UZ Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium

    Karoline Spaepen, Sigrid Stroobants, Patrick Dupont, Guy Bormans & Luc Mortelmans

  2. Rega Institute, Katholieke Universiteit, Leuven, Belgium

    Jan Balzarini

  3. Department of Hematology, UZ Gasthuisberg, Leuven, Belgium

    Gregor Verhoef & Peter Vandenberghe

  4. Department of Pathology, UZ Gasthuisberg, Leuven, Belgium

    Christine De Wolf-Peeters

Authors
  1. Karoline Spaepen
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  2. Sigrid Stroobants
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  3. Patrick Dupont
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  4. Guy Bormans
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  5. Jan Balzarini
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  6. Gregor Verhoef
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  7. Luc Mortelmans
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  8. Peter Vandenberghe
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  9. Christine De Wolf-Peeters
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Correspondence to Luc Mortelmans.

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Spaepen, K., Stroobants, S., Dupont, P. et al. [18F]FDG PET monitoring of tumour response to chemotherapy: does [18F]FDG uptake correlate with the viable tumour cell fraction?. Eur J Nucl Med Mol Imaging 30, 682–688 (2003). https://doi.org/10.1007/s00259-003-1120-6

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  • DOI: https://doi.org/10.1007/s00259-003-1120-6

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