title: Contrast-enhanced ultrasound with perflubutane in the assessment of anti-angiogenic effects: early prediction of the anticancer activity of bevacizumab in a mouse xenografted model.
abstract: To investigate the feasibility of contrast-enhanced ultrasound (CEUS) with perflubutane for evaluating anti-angiogenic effects, we assessed the contrast enhancement of mice xenograft treated with bevacizumab. SJSA-1 implanted mice were imaged before and 2, 6, 9 and 13 d after initiation of bevacizumab or saline treatment. Intra-tumoral perfusion areas were quantified by binarizing the ultrasound images and the micro-vessel density was observed by CD31 immunohistochemistry. As a result, the perfusion area and its ratio in the tumor were smaller in the bevacizumab group than the control group at 9 and 13 d, although tumor size was not significantly different. CD31-positive areas were smaller in the bevacizumab group than the control group and correlated well with the ratio of intra-tumoral perfusion areas. CEUS with perflubutane was found to have potential for early prediction of the anti-cancer activity of bevacizumab, and the perfusion area measured by binarized ultrasound images could be used as an indicator.
authors.affiliation: Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan. Electronic address: watanabe.rira.vi@daiichisankyo.co.jp.
authors.forename: Rira
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Munemasa
authors.affiliation: Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Matsumura
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003287:Contrast Media; D055088:Early Detection of Cancer / Q000379:methods*; D005240:Feasibility Studies; D005466:Fluorocarbons; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003287:Contrast Media; D005466:Fluorocarbons; D000068258:Bevacizumab; C108042:perfluorobutane
keywords: Bevacizumab; Contrast-enhanced ultrasound; Mice; Microbubble; Perflubutane; Sonazoid; Ultrasound; Xenograft