title: In vivo imaging of eribulin-induced reoxygenation in advanced breast cancer patients: a comparison to bevacizumab.
abstract: BACKGROUND
  Eribulin mesylate (eribulin) is a first-in-class halichondrin B-based microtubule dynamics inhibitor. To compare the anti-angiogenic activity of eribulin to that of bevacizumab, we compared tumour vessel remodelling and reoxygenation between the two agents.
  
  
  METHODS
  Patients with advanced breast cancer with stage III/IV were eligible for the study. Patients were assigned to receive either eribulin or single-agent bevacizumab. Tissue concentrations of oxyhaemoglobin (O2Hb) and deoxyhaemoglobin (HHb), and oxygen saturation (SO2) of breast tumours before and day 7 after the first infusion were repeatedly measured using diffuse optical spectroscopic imaging (DOSI). A pair of blood samples was collected for multiplex biomarker studies.
  
  
  RESULTS
  Baseline DOSI measurement of all 29 patients (eribulin, n=14 and bevacizumab, n=15) revealed significantly higher tumour concentrations of O2Hb and HHb than that in the normal breast tissue. After eribulin treatment, DOSI revealed a significant decrease in HHb concentration and increased SO2 during the observation period. This trend was not observed for bevacizumab. Instead, bevacizumab significantly decreased the concentration of O2Hb. The multiplex biomarker study revealed that both eribulin and bevacizumab decreased plasma concentrations of VEGF and bFGF, but only eribulin treatment suppressed the plasma concentration of TGF-β1.
  
  
  CONCLUSIONS
  Eribulin, but not bevacizumab, treatment increased tumour SO2. Suppression of TGF-β1 by eribulin could have a favourable anti-angiogenic effect. Our results suggest that differences in vascular remodelling between these two agents may account for their different effects on tumour reoxygenation.
authors.affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, 1371-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, 1371-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, 1371-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, 1371-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shigekawa
authors.affiliation: Department of Nuclear Medicine, International Medical Center, Saitama Medical University, 1371-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Department of Nuclear Medicine, International Medical Center, Saitama Medical University, 1371-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Ichiei
authors.initials: I
authors.lastname: Kuji
authors.affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, 1371-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Osaki
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005663:Furans / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007659:Ketones / Q000627:therapeutic use*; D009363:Neoplasm Proteins / Q000097:blood; D010100:Oxygen / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000032:analysis; D017239:Paclitaxel / Q000008:administration & dosage; D019265:Spectroscopy, Near-Infrared; D053773:Transforming Growth Factor beta1 / Q000097:blood; D050257:Tubulin Modulators / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000095662:Polyether Polyketides
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D000068258:Bevacizumab; D016222:Fibroblast Growth Factor 2; D005663:Furans; D006454:Hemoglobins; D007659:Ketones; D009363:Neoplasm Proteins; D010100:Oxygen; D010108:Oxyhemoglobins; D017239:Paclitaxel; D053773:Transforming Growth Factor beta1; D050257:Tubulin Modulators; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human; C100003:deoxyhemoglobin; C490954:eribulin; D000095662:Polyether Polyketides