Use of VEGFR-2 Targeted Ultrasound Contrast Agent for the Early Evaluation of Response to Sorafenib in a Mouse Model of Hepatocellular Carcinoma

Toaldo, Marco Baron; Salvatore, Veronica; Marinelli, Sara; Palamà, C.; Milazzo, Maddalena; Croci, Luca; Venerandi, Laura; Cipone, Mario; Bolondi, Luigi; Piscaglia, Fabio

doi:10.1007/s11307-014-0764-x

Cited by 51 publications

(33 citation statements)

References 28 publications

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“…Among those imaging modalities ultrasound is advantageous due to its wide availability and relatively low cost allowing to perform repetitive exams during the course of treatment, in particular during the early course of treatment, to assess whether early changes of imaging signal may be predictive of treatment response. With the use of molecularly targeted contrast microbubbles, 2D USMI has been shown to be feasible for monitoring tumor anti-angiogenic treatment (13,14). However, one of the major limitations of 2D USMI in monitoring tumor response compared to whole body imaging modalities such as CT, MRI, or PET is the limited field of view only representing a small fraction of the imaged tumor volumes.…”

Section: Discussionmentioning

confidence: 99%

“…Ultrasound molecular imaging (USMI) using contrast microbubbles targeted at molecular markers expressed on the tumor neovasculature is emerging as a promising tool to assess expression levels of angiogenic markers such as VEGFR2 for earlier cancer detection (9–12) and monitoring anti-angiogenic therapy (13,14). USMI combines the advantages of ultrasound such as relatively low cost, wide availability and portability, and lack of ionizing radiation with those of molecular imaging to allow quantitative monitoring of disease processes at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

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VEGFR2-Targeted Three-Dimensional Ultrasound Imaging Can Predict Responses to Antiangiogenic Therapy in Preclinical Models of Colon Cancer

et al. 2016

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Three-dimensional (3D) imaging capabilities to assess responses to anticancer therapies are needed to minimize sampling errors common to two-dimensional approaches as a result of spatial heterogeneity in tumors. Recently, the feasibility and reproducibility of 3D ultrasound molecular imaging (USMI) using contrast agents which target molecular markers has greatly improved, due to the development of clinical 3D matrix array transducers. Here we report preclinical proof of concept studies showing that 3DUSMI of VEGFR2/KDR expression accurately gauge longitudinal treatment responses to anti-angiogenesis therapy, in responding versus non-responding mouse models of colon cancer. Tumors in these models exhibited differential patterns of VEGFR2-targeted 3DUSMI signals during the course of anti-angiogenic treatment with bevacizumab. In responding tumors, the VEGFR2 signal decreased as soon as 24 hours after therapy was started, whereas in non-responding tumors there was no change in signal at any time point. The early decrease in VEGFR2 signal was highly predictive of treatment outcome at the end of therapy. Our results offer a preclinical proof that 3DUSMI can predict responses to anti-angiogenic therapy, warranting further investigation of its clinical translatability to predicting treatment outcomes in patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

VEGFR2-Targeted Three-Dimensional Ultrasound Imaging Can Predict Responses to Antiangiogenic Therapy in Preclinical Models of Colon Cancer

et al. 2016

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“…UMI has also proven its ability to detect biomarkers of early response to chemotherapy in several cancer types by MBs targeted to single biomarker expressions (VEGFR2, a V b 3 , endoglin, Annexin V, or VEGF-VEGFR complex) [24,[166][167][168][169] and MBs targeted to two or more of these biomarker expressions [142]. Impressively, studies have shown that UMI using a v b 3 -tMBs is a consistent method that can classify a tumour as a responder or a non-responder as early as two days after treatment [170,171].…”

Section: In Vivo Molecular Imagingmentioning

confidence: 99%

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Rooij

Daeichin

Skachkov

et al. 2015

International Journal of Hyperthermia

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Ultrasound contrast agents (UCAs) are used routinely in the clinic to enhance contrast in ultrasonography. More recently, UCAs have been functionalised by conjugating ligands to their surface to target specific biomarkers of a disease or a disease process. These targeted UCAs (tUCAs) are used for a wide range of pre-clinical applications including diagnosis, monitoring of drug treatment, and therapy. In this review, recent achievements with tUCAs in the field of molecular imaging, evaluation of therapy, drug delivery, and therapeutic applications are discussed. We present the different coating materials and aspects that have to be considered when manufacturing tUCAs. Next to tUCA design and the choice of ligands for specific biomarkers, additional techniques are discussed that are applied to improve binding of the tUCAs to their target and to quantify the strength of this bond. As imaging techniques rely on the specific behaviour of tUCAs in an ultrasound field, it is crucial to understand the characteristics of both free and adhered tUCAs. To image and quantify the adhered tUCAs, the state-of-the-art techniques used for ultrasound molecular imaging and quantification are presented. This review concludes with the potential of tUCAs for drug delivery and therapeutic applications.

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“…Indeed, potentially non-immunogenic targeted microbubbless have been developed (BR55 ® ; Bracco Imaging, Switzerland). So far, the only human applications include an experimental phase 0 study on prostate cancer, but preclinical results are very promising [69], especially in the field of response to antiangiogenic treatment. However, once approved for clinical use, molecular CEUS may improve HCC diagnosis or residual activity detection after locoregional treatments, widening the horizons of CEUS.…”

Section: Guidance and Evaluation Of Hcc Treatmentsmentioning

confidence: 99%

Imaging Diagnosis of Hepatocellular Carcinoma: Recent Advances of Contrast-Enhanced Ultrasonography with SonoVue®

et al. 2015

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Due to the ability to detect the typical contrast-imaging pattern for hepatocellular carcinoma (HCC), that is hyperenhancement in the arterial phase and hypoenhancement in the late phase on a cirrhotic background, contrast-enhanced ultrasonography (CEUS) was included in the American diagnostic algorithm for HCC in 2005. However, its role has been questioned because of the possibility of misdiagnosis of cholangiocarcinoma. The present review aims to describe the advantages and disadvantages of CEUS applications using Sonovue® for HCC. In particular there is focus on the accuracy of CEUS in detecting the typical HCC pattern, the CEUS patterns of intrahepatic cholangiocarcinoma (ICC), the risk of misdiagnosis with HCC, the diagnostic use of CEUS in cases of locoregional and systemic treatments, and the evaluation of response to antiangiogenic treatment using dedicated software.

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Use of VEGFR-2 Targeted Ultrasound Contrast Agent for the Early Evaluation of Response to Sorafenib in a Mouse Model of Hepatocellular Carcinoma

Abstract: BR55 appears to be useful in the prediction of response to sorafenib in a xenograft model of HCC.

Cited by 51 publications

References 28 publications

VEGFR2-Targeted Three-Dimensional Ultrasound Imaging Can Predict Responses to Antiangiogenic Therapy in Preclinical Models of Colon Cancer

VEGFR2-Targeted Three-Dimensional Ultrasound Imaging Can Predict Responses to Antiangiogenic Therapy in Preclinical Models of Colon Cancer

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Imaging Diagnosis of Hepatocellular Carcinoma: Recent Advances of Contrast-Enhanced Ultrasonography with SonoVue®

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