title: Early effects of low dose bevacizumab treatment assessed by magnetic resonance imaging.
abstract: BACKGROUND
  Antiangiogenic treatments have been shown to increase blood perfusion and oxygenation in some experimental tumors, and to reduce blood perfusion and induce hypoxia in others. The purpose of this preclinical study was to investigate the potential of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted MRI (DW-MRI) in assessing early effects of low dose bevacizumab treatment, and to investigate intratumor heterogeneity in this effect.
  
  
  METHODS
  A-07 and R-18 human melanoma xenografts, showing high and low expression of VEGF-A, respectively, were used as tumor models. Untreated and bevacizumab-treated tumors were subjected to DCE-MRI and DW-MRI before treatment, and twice during a 7-days treatment period. Tumor images of Ktrans (the volume transfer constant of Gd-DOTA) and ve (the fractional distribution volume of Gd-DOTA) were produced by pharmacokinetic analysis of the DCE-MRI data, and tumor images of ADC (the apparent diffusion coefficient) were produced from DW-MRI data.
  
  
  RESULTS
  Untreated A-07 tumors showed higher Ktrans, v e, and ADC values than untreated R-18 tumors. Untreated tumors showed radial heterogeneity in Ktrans, i.e., Ktrans was low in central tumor regions and increased gradually towards the tumor periphery. After the treatment, bevacizumab-treated A-07 tumors showed lower Ktrans values than untreated A-07 tumors. Peripherial tumor regions showed substantial reductions in Ktrans, whereas little or no effect was seen in central regions. Consequently, the treatment altered the radial heterogeneity in Ktrans. In R-18 tumors, significant changes in Ktrans were not observed. Treatment induced changes in tumor size, v e, and ADC were not seen in any of the tumor lines.
  
  
  CONCLUSIONS
  Early effects of low dose bevacizumab treatment may be highly heterogeneous within tumors and can be detected with DCE-MRI.
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Jon.Vidar.Gaustad@rr-research.no.
authors.forename: Jon-Vidar
authors.initials: JV
authors.lastname: Gaustad
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Trude.Golimo.Simonsen@rr-research.no.
authors.forename: Trude G
authors.initials: TG
authors.lastname: Simonsen
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Ragnhild.Smistad@rr-research.no.
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Smistad
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Catherine.Sem.Wegner@rr-research.no.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Wegner
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Lise.Mari.Klepp.Andersen@rr-research.no.
authors.forename: Lise Mari K
authors.initials: LM
authors.lastname: Andersen
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Einar.K.Rofstad@rr-research.no.
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000494:pharmacology*; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012878:Skin Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000068258:Bevacizumab