Early prediction of tumor response to bevacizumab treatment in murine colon cancer models using three-dimensional dynamic contrast-enhanced ultrasound imaging

Abstract

Due to spatial tumor heterogeneity and consecutive sampling errors, it is critically important to assess treatment response following antiangiogenic therapy in three dimensions as two-dimensional assessment has been shown to substantially over- and underestimate treatment response. In this study, we evaluated whether three-dimensional (3D) dynamic contrast-enhanced ultrasound (DCE-US) imaging allows assessing early changes in tumor perfusion following antiangiogenic treatment (Bevacizumab administered at a dose of 10 mg/kg b.w.), and whether these changes could predict treatment response in colon cancer tumors that either are responsive (LS174T tumors) or none responsive (CT26) to the propose treatment. Our results showed that the perfusion parameters of 3D DCE-US including peak enhancement (PE) and area under curve (AUC) significantly decreased by up to 69% and 77%, respectively, in LS174T tumors within 1 day after antiangiogenic treatment (P=0.005), but not in CT26 tumors (P>0.05). Similarly, the percentage area of neovasculature significantly decreased in treated vs. control LS174T tumors (P<0.001), but not in treated vs. control CT26 tumors (P=0.796). Early decrease in both PE and AUC by 45–50% were predictive of treatment response in 100% (95% CI, 69.2%, 100%) of responding tumors, and in 100% (95% CI, 88.4%, 100%) and 86.7% (95% CI, 69.3%, 96.2%), respectively, of nonresponding tumors. In conclusion, 3D DCE-US provides clinically relevant information on the variability of tumor response to antiangiogenic therapy and may be further developed as biomarker for predicting treatment outcomes.

Contrast-enhanced Ultrasound in evaluating of angiogenesis and tumor staging of nasopharyngeal carcinoma in nude mice

“…Meanwhile, the mean perfusion showed a similar increase. Some studies investigated the influence of angiogenesis on tumor growth by comparing the tumor microvasculature change after anti-angiogenic treatment, using CEUS imaging [31,37]. In the present study, we also found a positive correlation between tumor volume and MVD in NPC.…”

Quantitative Three-Dimensional Dynamic Contrast-Enhanced Ultrasound Imaging: First-In-Human Pilot Study in Patients with Liver Metastases

“…While technical limitations may hinder the use of 3D DCE-US to characterize complexities of vascular networks, particularly in tumors, this remains an active area of research and innovation. In line with this, pre-clinical studies have already demonstrated that 3D DCE-US allows reliable assessment of early treatment response and prediction of response after anti-angiogenic therapy in human colon cancer xenograft models in mice 17 , 19 - 22 . Several recent studies have examined the role of non-dynamic 3D contrast images for various clinical applications, including cancer imaging and management 23 - 31 .…”

Consensus guidelines for the use and interpretation of angiogenesis assays

“…Due to depth and/or the decreased transparency at later stages, PV has mainly been used in embryos or early larvae, although recent advances in confocal microscopy, ultrasound, and tomography tools [323] and methods have facilitated deeper imaging in more opaque tissues.…”