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

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, K_i. 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 (K_i). 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 K_i/flow and k₃/flow ratios with therapy. The ratio of ¹⁸F-FDG flux to transport (K_i/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.