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Title: Enhanced antitumor efficacy of a vascular disrupting agent combined with an antiangiogenic in a rat liver tumor model evaluated by multiparametric MRI
Authors: Chen, Feng ×
Feng, Yingmei
Zheng, Kaier
De Keyzer, Frederik
Li, Junjie
Feng, YUanbo
Cona, Marlein Miranda
Wang, Huaijun
Jiang, Yansheng
Yu, Jie
Marchal, Guy
Verfaillie, Catherine
De Geest, Bart
Oyen, Raymond
Ni, Yicheng #
Issue Date: 2012
Publisher: Public Library of Sciene
Series Title: PLoS One vol:7 issue:7
Article number: e41140
Abstract: A key problem in solid tumor therapy is tumor regrowth from a residual viable rim after treatment with a vascular disrupting agent (VDA). As a potential solution, we studied a combined treatment of a VDA and antiangiogenic. This study was approved by the institutional ethical committee for the use and care of laboratory animals. Rats with implanted liver tumors were randomized into four treatment groups: 1) Zd6126 (Zd); 2) Thalidomide (Tha); 3) Zd in combination with Tha (ZdTha); and 4) controls. Multiparametric MRIs were performed and quantified before and after treatment. Circulating endothelial progenitor cells (EPCs) and plasma stromal cell-derived factor-1α (SDF-1α) were monitored. Tumor apoptosis, necrosis, and microvessels were verified by histopathology. A single use of Zd or Tha did not significantly delay tumor growth. The combined ZdTha showed enhanced antitumor efficacy due to synergistic effects; it induced a cumulative tumor apoptosis or necrosis, which resulted in significant delay in tumor growth and reduction in the viable tumor rim; it also reduced tumor vessel permeability; and it improved tumor hemodynamic indexes, most likely via a transient normalization of tumor vasculature induced by Tha. A stepwise linear regression analysis showed that the apparent diffusion coefficient was an independent predictor of tumor growth. We found no significant increases in Zd-induced circulating EPCs or plasma SDF-1α. ZdTha showed improved therapeutic efficacy in solid tumors compared to either agent alone. The therapeutic effects were successfully tracked in vivo with multiparametric MRI.
URI: 
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Theragnostic Laboratory (+)
Radiology
× corresponding author
# (joint) last author

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