title: Dynamic (18)F-FDG-PET for monitoring treatment effect following anti-angiogenic therapy in triple-negative breast cancer xenografts.
abstract: BACKGROUND
  Dynamic (18)F-FDG PET allows the study of glucose distribution in tissues as a function of time and space. Using pharmacokinetics, the temporal uptake pattern of (18)F-FDG may be separated into components reflecting perfusion and metabolism. Bevacizumab is an angiogenesis inhibitor which prevents the growth of new blood vessels, and may potentially lead to normalization of the blood circulation in the tumor. The purpose of the study was to explore the use of dynamic PET as a tool for monitoring treatment effect, reflected by changes in perfusion and metabolism.
  
  
  METHODS
  Twelve athymic nude mice, bearing the bilateral triple-negative human breast cancer xenograft MAS98.12 were treated with bevacizumab (5 mg/kg i.p.). Dynamic PET data was acquired prior to and 24 and 72 hours after treatment for 1 hour after injection of 10 MBq (18)F-FDG and fitted with a FDG two-tissue compartment model. The changes in the rate constants k1, k3, MRFDG and the vascular fraction νB were assessed. To evaluate the effect of treatment regimes, 30 mice, randomized in 5 groups, received either vehicle (0.9% NaCl), bevacizumab (5 mg/kg i.p.), doxorubicin (8 mg/kg i.v.) or bevacizumab and doxorubicin either together, or doxorubicin 24 hours after bevacizumab treatment. Tumor volume was measured twice a week.
  
  
  RESULTS
  The perfusion-related rate parameter k1 and the metabolic rate constant k3 decreased significantly 24 hours after treatment. This decrease was followed by an increase, albeit non-significant, at 72 hours post treatment. Doxorubicin given 24 hours after bevacizumab showed less antitumor effect compared to concomitant treatment.
  
  
  CONCLUSIONS
  Dynamic PET can detect changes in tumor perfusion and metabolism following anti-angiogenic therapy in mouse xenograft models. Longitudinal dynamic PET, used to assess the efficacy of anti-angiogenic treatment, can identify the time frame of potential tumor vasculature re-normalization and allow optimal timing of supplementary therapy (radiation or chemotherapy).
authors.affiliation: Department of Tumor Biology, Oslo University Hospital , Oslo , Norway.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Kristian
authors.forename: Mona Elisabeth
authors.initials: ME
authors.lastname: Revheim
authors.forename: Hong
authors.initials: H
authors.lastname: Qu
authors.forename: Gunhild M
authors.initials: GM
authors.lastname: Mælandsmo
authors.forename: Olav
authors.initials: O
authors.lastname: Engebråten
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
authors.forename: Eirik
authors.initials: E
authors.lastname: Malinen
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D064726:Triple Negative Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000068258:Bevacizumab; D004317:Doxorubicin