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

Research output: Contribution to journalArticle

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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
StatePublished - Nov 1 2004
Externally publishedYes

Fingerprint

Fluorodeoxyglucose F18
Breast Neoplasms
Drug Therapy
Neoplasms
Glucose
Water
Therapeutics
Phosphorylation
Phenotype

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.

18F-FDG kinetics in locally advanced breast cancer : Correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. / Tseng, Jeffrey; Dunnwald, Lisa K.; Schubert, Erin K.; Link, Jeanne; Minoshima, Satoshi; Muzi, Mark; Mankoff, David A.

In: Journal of Nuclear Medicine, Vol. 45, No. 11, 01.11.2004, p. 1829-1837.

Research output: Contribution to journalArticle

Tseng, J, Dunnwald, LK, Schubert, EK, Link, J, Minoshima, S, Muzi, M & Mankoff, DA 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, vol. 45, no. 11, pp. 1829-1837.
Tseng, Jeffrey ; Dunnwald, Lisa K. ; Schubert, Erin K. ; Link, Jeanne ; Minoshima, Satoshi ; Muzi, Mark ; Mankoff, David A. / 18F-FDG kinetics in locally advanced breast cancer : Correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. In: Journal of Nuclear Medicine. 2004 ; Vol. 45, No. 11. pp. 1829-1837.
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title = "18F-FDG kinetics in locally advanced breast cancer: Correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy",
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.",
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AU - Muzi, Mark

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N2 - 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.

AB - 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.

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