Abstract

Due to a lack of data on predictors of electroporation-based treatment outcomes, we investigated the potential predictive role of contrast-enhanced harmonic ultrasound (CEUS) in mice B16F10 melanoma treated by gene electrotransfer (GET) to silence melanoma cell adhesion molecule (MCAM) and radiotherapy, which has not been evaluated yet. CEUS evaluation was verified by tumor histological analysis. Mice bearing subcutaneous tumors were treated with GET to silence MCAM, irradiation or the combination of GET to silence MCAM and irradiation (combined treatment). CEUS of the tumors used to evaluate tumor perfusion was performed before and up to 10 days after the beginning of the experiment, and the CEUS results were compared with tumor growth and the number of blood vessels analyzed in the histological tumor sections. CEUS revealed a decrease in tumor perfusion in the combined therapy groups compared with the control groups and correlated with tumor histological analyses, which showed a decreased vascular density. In this study a trend of inverse correlation was observed between tumor perfusion and treatment efficacy. The greater the perfusion of the tumor, the shorter the expected doubling time. Furthermore, decreased perfusion showed a trend to correlate with higher antitumor efficacy. Thus, CEUS could be used to predict tumoral vascular density and treatment effectiveness.

Highlights

  • The tumor vasculature is an attractive target for cancer therapy.A single vessel facilitates the survival of multiple tumor cells and provides the main route for metastatic spread [1]

  • Due to a lack of data on predictors of electroporation-based treatment outcomes, we investigated the potential predictive role of contrast-enhanced harmonic ultrasound (CEUS) in mice B16F10 melanoma treated by gene electrotransfer (GET) to silence melanoma cell adhesion molecule (MCAM) and radiotherapy, which has not been evaluated yet

  • To evaluate the capacity of CEUS to assess tumor perfusion/vascularization and outcome following electroporation treatment, we used mice bearing B16F10 melanoma tumors subjected to electroporation gene therapy and ionizing radiation as a that was previously observed to be a relevant model [18], where different levels of response were determined after monotherapies and after the combined treatment with radiation therapy

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Summary

Introduction

The tumor vasculature is an attractive target for cancer therapy. A single vessel facilitates the survival of multiple tumor cells and provides the main route for metastatic spread [1]. Tumor vessel density and certain tumor perfusion aspects have been intensively investigated as possible predictors of tumor behavior and treatment outcome. A method to detect tissue perfusion at the capillary level is contrast-enhanced harmonic ultrasound (CEUS). It was shown to be an accurate predictor of tumor vascularization compared with histological results [2,3,4], and it correlated with advanced diagnostic imaging methods [5]. CEUS proved to be valuable in assessing the

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