title: Dynamic 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts.
abstract: Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancer patients. We employed dynamic 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG PET) to evaluate changes in three breast cancer xenograft lines in mice following three chemotherapy regimens.
  
  
  
  Sixty-six athymic nude mice bearing bilateral breast cancer xenografts (two basal-like and one luminal-like subtype) underwent three 60 min [18F]FDG PET scans. Scans were performed prior to and 3 and 10 days after treatment with doxorubicin, paclitaxel, or carboplatin. Tumor growth was monitored in parallel. A pharmacokinetic compartmental model was fitted to the tumor uptake curves, providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Early and late standardized uptake values (SUVEand SUVL, respectively); the rate constants k1, k2, and k3, and the intravascular fraction vBwere estimated. Changes in tumor volume were used as a response measure. Multivariate partial least-squares regression (PLSR) was used to assess if PET parameters could model tumor response and to identify PET parameters with the largest impact on response.
  
  
  
  Treatment responders had significantly larger perfusion-related parameters (k1and k2) and lower metabolism-related parameter (k3) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k1and k2at day 10 and changes in k3explained most of the variability in response to therapy, whereas SUVLand particularly SUVEwere of lesser importance.
  
  
  
  Overall, rate parameters related to both tumor perfusion and metabolism were associated with tumor response. Conventional metrics of [18F]FDG uptake such as SUVEand SUVLapparently had little relation to tumor response, thus necessitating full dynamic scanning and pharmacokinetic analysis for optimal evaluation of chemotherapy-induced changes in breast cancers.
authors.affiliation: Department of Tumor Biology, Oslo University Hospital, Oslo, Norway.|K.G. Jebsen Center for Breast Cancer Research, University of Oslo, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Kristian
authors.affiliation: The Intervention Centre, Oslo University Hospital, Oslo, Norway.
authors.forename: Jon Erik
authors.initials: JE
authors.lastname: Holtedahl
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Turid
authors.initials: T
authors.lastname: Torheim
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Futsaether
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Eivor
authors.initials: E
authors.lastname: Hernes
authors.affiliation: Department of Tumor Biology, Oslo University Hospital, Oslo, Norway.|K.G. Jebsen Center for Breast Cancer Research, University of Oslo, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Engebraaten
authors.affiliation: Department of Tumor Biology, Oslo University Hospital, Oslo, Norway.|K.G. Jebsen Center for Breast Cancer Research, University of Oslo, Oslo, Norway.|Department of Pharmacy, University of Tromsø, Tromsø, Norway.
authors.forename: Gunhild M
authors.initials: GM
authors.lastname: Mælandsmo
authors.affiliation: Department of Physics, University of Oslo, Oslo, Norway. eirik.malinen@fys.uio.no.|Department of Medical Physics, Oslo University Hospital, Oslo, Norway. eirik.malinen@fys.uio.no.
authors.forename: Eirik
authors.initials: E
authors.lastname: Malinen
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008819:Mice, Nude; D000072078:Positron Emission Tomography Computed Tomography; D049268:Positron-Emission Tomography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: 2-deoxy-2-[18F]fluoro-D-glucose; Breast cancer; Chemotherapy; Partial least-squares regression; Pharmacokinetic analysis; Positron emission tomography