18F-FDG kinetics in locally advanced breast cancer: Correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy

Jeffrey Tseng, Lisa K. Dunnwald, Erin K. Schubert, Jeanne Link, Satoshi Minoshima, Mark Muzi, David A. Mankoff

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96 Scopus citations

Abstract

The aim of this study was to characterize the biologic response of locally advanced breast cancer (LABC) to chemotherapy using 15O-water-derived blood flow measurements and 18F-FDG-derived glucose metabolism rate parameters. Methods: Thirty-five LABC patients underwent PET with 15O-water and 18F-FDG before neoadjuvant chemotherapy and 2 mo after the initiation of treatment. Kinetic analysis for 15O-water was performed using a single tissue compartment model to calculate blood flow; a 2-tissue compartment model was used to estimate 18F-FDG rate parameters K1, k2, k3, and the flux constant, Ki. Correlations and ratios between blood flow and 18F-FDG rate parameters were calculated and compared with pathologic tumor response. Results: Although blood flow and 18F-FDG transport (K1) were correlated before chemotherapy, there was relatively poor correlation between blood flow and the phosphorylation constant (k3) or the overall 18F-FDG flux (Ki). Blood flow and 18F-FDG flux were more closely matched after chemotherapy, with changes in k3 accounting for the increased correlation. These findings were consistent with a decline in both the Ki/flow and k3/flow ratios with therapy. The ratio of 18F-FDG flux to transport (Ki/K1) after 2 mo of chemotherapy was predictive of ultimate response. Conclusion: The pattern of tumor glucose metabolism in LABC, as reflected by analysis of 18F-FDG rate parameters, changes after therapy, even in patients with modest clinical responses. This may indicate a change in tumor "metabolic phenotype" in response to treatment. A low ratio of glucose metabolism (reflected by K i) to glucose delivery (reflected by K1 and blood flow) after therapy is associated with a favorable response. Further work is needed to understand the tumor biology underlying these findings.

Original languageEnglish (US)
Pages (from-to)1829-1837
Number of pages9
JournalJournal of Nuclear Medicine
Volume45
Issue number11
Publication statusPublished - Nov 1 2004
Externally publishedYes

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Keywords

  • O-water
  • F-FDG
  • Blood flow
  • Breast cancer
  • Kinetic analysis
  • PET
  • Response to therapy
  • Tumor biology

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Tseng, J., Dunnwald, L. K., Schubert, E. K., Link, J., Minoshima, S., Muzi, M., & Mankoff, D. A. (2004). 18F-FDG kinetics in locally advanced breast cancer: Correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. Journal of Nuclear Medicine, 45(11), 1829-1837.