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 (15)O-water-derived blood flow measurements and (18)F-FDG-derived glucose metabolism rate parameters.


METHODS
Thirty-five LABC patients underwent PET with (15)O-water and (18)F-FDG before neoadjuvant chemotherapy and 2 mo after the initiation of treatment. Kinetic analysis for (15)O-water was performed using a single tissue compartment model to calculate blood flow; a 2-tissue compartment model was used to estimate (18)F-FDG rate parameters K(1), k(2), k(3), and the flux constant, K(i). Correlations and ratios between blood flow and (18)F-FDG rate parameters were calculated and compared with pathologic tumor response.


RESULTS
Although blood flow and (18)F-FDG transport (K(1)) were correlated before chemotherapy, there was relatively poor correlation between blood flow and the phosphorylation constant (k(3)) or the overall (18)F-FDG flux (K(i)). Blood flow and (18)F-FDG flux were more closely matched after chemotherapy, with changes in k(3) accounting for the increased correlation. These findings were consistent with a decline in both the K(i)/flow and k(3)/flow ratios with therapy. The ratio of (18)F-FDG flux to transport (K(i)/K(1)) after 2 mo of chemotherapy was predictive of ultimate response.


CONCLUSIONS
The pattern of tumor glucose metabolism in LABC, as reflected by analysis of (18)F-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 K(1) and blood flow) after therapy is associated with a favorable response. Further work is needed to understand the tumor biology underlying these findings.
Tseng
Jeffrey
J
Division of Nuclear Medicine, Department of Radiology, University of Washington, Seattle, Washington 98195-6113, USA.
Dunnwald
Lisa K
LK
Schubert
Erin K
EK
Link
Jeanne M
JM
Minoshima
Satoshi
S
Muzi
Mark
M
Mankoff
David A
DA
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001783:Blood Flow Velocity; D001940:Breast / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007700:Kinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013223:Statistics as Topic; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose