Noninvasive Contrast-enhanced US Quantitative Assessment of Tumor Microcirculation in a Murine Model: Effect of Discontinuing Anti-VEGF Therapy

Abstract

Purpose:To determine, by using contrast material-enhanced ultrasonography (US), how quickly renal tumors grafted in mice begin to revascularize after stopping bevacizumab treatment. Materials and Methods:All experiments were approved by the regional ethics committee. A human tumor cell line SK-NEP-1 was grafted at day 0 in the left kidney of 50 nude mice. Forty-two mice developed tumors and longitudinal follow-up was performed on 32 surviving mice. From day 13, 14 controls received biweekly saline; 11 mice received biweekly bevacizumab until day 35 (continuous); and seven received biweekly bevacizumab until day 22, then biweekly placebo until day 35 (discontinued). Contrast-enhanced US was performed on days 13, 14, 22, 27, and 35. Once the injected contrast material distribution reached an equilibrium phase, highacoustic pressure pulses were applied to destroy microbubbles in the capillary bed in the imaged plane. Reperfusion was monitored, and time-signal intensity (SI) curves were obtained from the linear average of SIs in intratumoral and matched-depth renal cortex regions of interest. A kinetic parameter calculated from reperfusion curves refl ects local perfusion, normalized with respect to adjacent renal cortex perfusion. Normalized perfusion obtained from each group was compared with that from the other groups and with necrosis percentages and microvascular density assessed histologically at day 35. Comparisons were made by using analyses of variance and Tukey-Kramer tests.

Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma

“…The current low-mechanical-index techniques for CEUS are capable of real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules, from which timeintensity curves can be obtained by means of analytic software and then a series of semi-quantitative perfusion measurements extracted and analysed [9][10][11]. This method has shown a possible benefit in diagnosing FNH by enabling analysis of the quantitative parametric curves of the five types of hypervascular liver lesions [9].…”

Assessment of Early Tumor Response to Cytotoxic Chemotherapy With Dynamic Contrast-Enhanced Ultrasound in Human Breast Cancer Xenografts

“…CEUS offers great advantages of evaluating tumor perfusion in real time compared to other methods for assessing tumor blood perfusion. Quantitative evaluation of tumor perfusion with CEUS has been used to evaluate tumor response to antiangiogenic agents which work by typically preventing the development of new blood vessels needed to support tumor growth both in animal [8][9][10][11] and clinical [32,33] studies, and preliminary results were promising. In this study, the early treatment effect of a cytotoxic chemotherapeutic drug, adriamycin, was evaluated with CEUS for the first time, and decrease in tumor perfusion was detected by CEUS in treated tumors as early as 2 days after therapy, whereas measurable tumor shrinkage with significance difference in the volume was noticed 6 days after treatment, which gives a great potential for this technique to assess early tumor response to therapy in future preclinical and clinical studies.…”

“…Contrast-enhanced ultrasound (CEUS) offers the major advantages of evaluating tumor perfusion in real time and minimal invasiveness when compared to other methods for assessment of tumor perfusion. Quantification of tumor perfusion with CEUS has been studied to assess tumor response to antiangiogenic therapy, and preliminary results were promising [8][9][10][11]. Other than these molecular target drugs, currently most of the cancer patents still undergo the treatment of cytotoxic chemotherapy.…”

Functional imaging assessment of anti-angiogenic therapies: what is its place in 2012?

“…Il a été ainsi démontré expérimentale-ment en IRM que la perméabilité capillaire est dépendante de l'expression du VEGF [40] et que sous l'action d'un facteur anti-VEGF, c'est la perméabilité capillaire aux macromolécules qui diminue alors que le volume sanguin (BV) reste inchangé [6,40]. En IRM, en TDM ou en échographie de contraste, il est possible d'identifier des modifications de la perfusion tumorale qui précédent les modifications en taille de tumeurs humaines implantées sur des modèles animaux traités par thérapies ciblées [11,18,21]. En pratique clinique, une réduction significative de K trans et de l'IAUGC dans des études qui utilisaient le bevacizumab, l'AG 013736, le BIBF 1120 ou l'AZD 2171 a été retrouvée [37].…”