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Dynamic 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts

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Abstract

Purpose

Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancer patients. We employed dynamic 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG PET) to evaluate changes in three breast cancer xenograft lines in mice following three chemotherapy regimens.

Procedures

Sixty-six athymic nude mice bearing bilateral breast cancer xenografts (two basal-like and one luminal-like subtype) underwent three 60 min [18F]FDG PET scans. Scans were performed prior to and 3 and 10 days after treatment with doxorubicin, paclitaxel, or carboplatin. Tumor growth was monitored in parallel. A pharmacokinetic compartmental model was fitted to the tumor uptake curves, providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Early and late standardized uptake values (SUVE and SUVL, respectively); the rate constants k 1, k 2, and k 3, and the intravascular fraction v B were estimated. Changes in tumor volume were used as a response measure. Multivariate partial least-squares regression (PLSR) was used to assess if PET parameters could model tumor response and to identify PET parameters with the largest impact on response.

Results

Treatment responders had significantly larger perfusion-related parameters (k 1 and k 2) and lower metabolism-related parameter (k 3) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k 1 and k 2 at day 10 and changes in k 3 explained most of the variability in response to therapy, whereas SUVL and particularly SUVE were of lesser importance.

Conclusions

Overall, rate parameters related to both tumor perfusion and metabolism were associated with tumor response. Conventional metrics of [18F]FDG uptake such as SUVE and SUVL apparently had little relation to tumor response, thus necessitating full dynamic scanning and pharmacokinetic analysis for optimal evaluation of chemotherapy-induced changes in breast cancers.

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Acknowledgments

Financial support received from the K.G. Jebsen Center for Breast Cancer Research is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Tumor Biology, Oslo University Hospital, Oslo, Norway

    Alexandr Kristian, Olav Engebraaten & Gunhild M. Mælandsmo

  2. K.G. Jebsen Center for Breast Cancer Research, University of Oslo, Oslo, Norway

    Alexandr Kristian, Olav Engebraaten & Gunhild M. Mælandsmo

  3. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Alexandr Kristian & Olav Engebraaten

  4. The Intervention Centre, Oslo University Hospital, Oslo, Norway

    Jon Erik Holtedahl

  5. Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway

    Turid Torheim & Cecilia Futsaether

  6. Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway

    Eivor Hernes

  7. Department of Oncology, Oslo University Hospital, Oslo, Norway

    Olav Engebraaten

  8. Department of Pharmacy, University of Tromsø, Tromsø, Norway

    Gunhild M. Mælandsmo

  9. Department of Physics, University of Oslo, Oslo, Norway

    Eirik Malinen

  10. Department of Medical Physics, Oslo University Hospital, Oslo, Norway

    Eirik Malinen

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  1. Alexandr Kristian
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  2. Jon Erik Holtedahl
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Correspondence to Eirik Malinen.

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Kristian, A., Holtedahl, J.E., Torheim, T. et al. Dynamic 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts. Mol Imaging Biol 19, 271–279 (2017). https://doi.org/10.1007/s11307-016-0998-x

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  • DOI: https://doi.org/10.1007/s11307-016-0998-x

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