Molecular Imaging and Biology

, Volume 19, Issue 2, pp 271–279

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

  • Alexandr Kristian
  • Jon Erik Holtedahl
  • Turid Torheim
  • Cecilia Futsaether
  • Eivor Hernes
  • Olav Engebraaten
  • Gunhild M. Mælandsmo
  • Eirik Malinen
Research Article

DOI: 10.1007/s11307-016-0998-x

Cite this article as:
Kristian, A., Holtedahl, J.E., Torheim, T. et al. Mol Imaging Biol (2017) 19: 271. doi:10.1007/s11307-016-0998-x

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 k1, k2, and k3, and the intravascular fraction vB 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 (k1 and k2) and lower metabolism-related parameter (k3) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k1 and k2 at day 10 and changes in k3 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.

Key words

Positron emission tomography Breast cancer Chemotherapy 2-deoxy-2-[18F]fluoro-D-glucose Pharmacokinetic analysis Partial least-squares regression 

Copyright information

© World Molecular Imaging Society 2016

Authors and Affiliations

  • Alexandr Kristian
    • 1
    • 2
    • 3
  • Jon Erik Holtedahl
    • 4
  • Turid Torheim
    • 5
  • Cecilia Futsaether
    • 5
  • Eivor Hernes
    • 6
  • Olav Engebraaten
    • 1
    • 2
    • 3
    • 7
  • Gunhild M. Mælandsmo
    • 1
    • 2
    • 8
  • Eirik Malinen
    • 9
    • 10
  1. 1.Department of Tumor BiologyOslo University HospitalOsloNorway
  2. 2.K.G. Jebsen Center for Breast Cancer ResearchUniversity of OsloOsloNorway
  3. 3.Institute of Clinical MedicineUniversity of OsloOsloNorway
  4. 4.The Intervention CentreOslo University HospitalOsloNorway
  5. 5.Department of Mathematical Sciences and TechnologyNorwegian University of Life SciencesÅsNorway
  6. 6.Department of Radiology and Nuclear MedicineOslo University HospitalOsloNorway
  7. 7.Department of OncologyOslo University HospitalOsloNorway
  8. 8.Department of PharmacyUniversity of TromsøTromsøNorway
  9. 9.Department of PhysicsUniversity of OsloOsloNorway
  10. 10.Department of Medical PhysicsOslo University HospitalOsloNorway