VEGFR2-Targeted Contrast-Enhanced Ultrasound to Distinguish between Two Anti-Angiogenic Treatments

作者: Thomas Payen , Alexandre Dizeux , Capucine Baldini , Delphine Le Guillou-Buffello , Michele Lamuraglia

DOI: 10.1016/J.ULTRASMEDBIO.2015.04.010

关键词: ImmunostainingPharmacologyContrast-enhanced ultrasoundNecrosisUltrasoundImatinibKinase insert domain receptorPathologyPlaceboSunitinibMedicine

摘要: The aim of this study was to evaluate the capacity BR55, an ultrasound contrast agent specifically targeting vascular endothelial growth factor receptor 2 (VEGFR2), distinguish specific anti-VEGFR2 therapy effect sunitinib from other anti-angiogenic effects a (imatinib) that does not directly inhibit VEGFR2. Sunitinib, imatinib and placebo were administered daily for 11 d (264 h) 45 BalbC mice bearing ectopic CT26 murine colorectal carcinomas. During course therapy, B-mode ultrasound, contrast-enhanced VEGFR2-targeted performed assess tumor morphology, vascularization VEGFR2 expression, respectively. angiogenic on these three aspects characterized using volume, area differential targeted enhancement. Necrosis, microvasculature expression also determined by histology immunostaining. B-Mode imaging revealed significantly decreased in sunitinib-treated at day (p < 0.05), whereas did affect growth. Functional evaluation 0.02) similar amounts under both treatments 8 (192 h): −23% −21% sunitinib. No significant decrease observed group. Targeted lower enhancement, is, levels relative placebo-treated 24 h 0.05) placebo- imatinib-treated 48 0.05). Histologic assessment tumors after final indicated necrotic higher group (21%) than (8%, p 0.001) (11%, groups. able sensitively differentiate reduced with functional flow produced agents. BR55 molecular was, thus, detect early therapeutic response as soon beginning treatment provide discrimination (48 between during acting receptor.

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