Abstract
PurposeTo evaluate quantitative and semi-quantitative ultrasound molecular imaging (USMI) for antiangiogenic therapy monitoring in human colon cancer xenografts in mice.ProceduresColon cancer was established in 17 mice by injection of LS174T (Nr = 9) or CT26 (Nn = 8) cancer cells to simulate clinical responders and non-responders, respectively. Antiangiogenic treatment (bevacizumab; Nrt = Nnt = 5) or control treatment (saline; Nrc = 4, Nnc = 3) was administered at days 0, 3, and 7. Three-dimensional USMI was performed by injection at days 0, 1, 3, 7, and 10 of microbubbles targeted to the vascular endothelial growth factor receptor 2 (VEGFR2). Microbubble binding rate (kb), estimated by first-pass binding model fitting, and semi-quantitative parameters late enhancement (LE) and differential targeted enhancement (dTE) were compared at each day to evaluate their ability to assess and predict the response to therapy. Correlation analysis with the ex-vivo immunohistological quantification of VEGFR2 expression and the percentage blood vessel area was also performed.ResultsSignificant changes in the USMI parameters during treatment were observed only in the responders treated with bevacizumab (p-value < 0.05). Prediction of the response to therapy as early as 1 day after treatment was achieved by the quantitative parameter kb (p-value < 0.01), earlier than possible by tumor volume quantification. USMI parameters could significantly distinguish between clinical responders and non-responders (p-value << 0.01) and correlated well with the ex-vivo quantification of VEGFR2 expression and the percentage blood vessels area (p-value << 0.01).ConclusionUSMI (semi)quantitative parameters provide earlier assessment of the response to therapy compared to tumor volume, permit early prediction of non-responders, and correlate well with ex-vivo angiogenesis biomarkers.
Highlights
Cancer is one of the leading causes of death worldwide and represents a major health challenge, accounting for 8.8 million deaths in 2015—about 16 % global mortality [1]
Significant linear and rank correlation was found between all ultrasound molecular imaging (USMI) parameters and both vascular endothelial growth factor receptor 2 (VEGFR2) expression and the percentage blood vessel area, except for late enhancement (LE), for which the rank correlation with the percentage blood vessel area was not significant (Spearman ρs = 0.43, p-value = 0.09)
We evaluated semi-quantitative and quantitative USMI for assessment of the response to antiangiogenic treatment in two colon cancer mouse models, simulating clinical responders and non-responders
Summary
Cancer is one of the leading causes of death worldwide and represents a major health challenge, accounting for 8.8 million deaths in 2015—about 16 % global mortality [1]. Based on the established link between cancer growth and the process of angiogenesis [3, 4], i.e., the formation of a vascular network supporting tumor development, novel therapeutic strategies aim at blocking or disrupting specific angiogenic pathways [5,6,7]. Due to its ubiquitous overexpression, the vascular endothelial growth factor (VEGF) is the dominant target of antiangiogenic drugs. Several VEGF inhibitors are approved for first and second lines of treatment of different types of cancers in the USA and Europe. VEGF pathways represent one of the main targets for treatment of metastatic disease [6,7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
