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 (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.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Washington, Seattle, Washington 98195-6113, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Tseng
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Dunnwald
authors.forename: Erin K
authors.initials: EK
authors.lastname: Schubert
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Link
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minoshima
authors.forename: Mark
authors.initials: M
authors.lastname: Muzi
authors.forename: David A
authors.initials: DA
authors.lastname: Mankoff
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose