Dynamic contrast-enhanced magnetic resonance imaging at 1.5 Tesla with gadopentetate dimeglumine to assess the angiostatic effects of anginex in mice

Lussanet, de Qr; Beets-Tan, R. G. H.; Backes, WH Walter; Schaft, van der Dwj Daisy; Engelshoven, van Jma Jos; Mayo, KH; Griffioen, AW

doi:10.1016/j.ejca.2004.01.020

Cited by 31 publications

(33 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3d and h, the pixel-by-pixel analysis of the images before and after injection of the contrast agent is presented for visualization of the statistically significant signal increase. The MR imaging voxels that showed significant signal enhancement following RGD-pQDs injection were mainly found at the tumor periphery, which corresponds with the regions of the tumor with highest angiogenic activity [17]. In previous studies, we applied RGD-conjugated paramagnetic liposomes to visualize angiogenesis in tumor-bearing mice with molecular MRI and observed a similar pattern of signal enhancement in peripheral regions of the tumor [7,18].…”

Section: Resultsmentioning

confidence: 91%

Molecular imaging of tumor angiogenesis using αvβ3-integrin targeted multimodal quantum dots

et al. 2008

View full text Add to dashboard Cite

Molecular imaging of angiogenesis is urgently needed for diagnostic purposes such as early detection, monitoring of (angiostatic) therapy and individualized therapy. Multimodality molecular imaging is a promising and refined technique to study tumor angiogenesis, which has so far been largely unexplored due to the lack of suitable multimodal contrast agents. Here, we report on the application of a novel alphavbeta3-specific quantum dot-based nanoparticle, which has been optimized for both optical and magnetic resonance detection of tumor angiogenesis. Upon intravenous injection of RGD-pQDs in tumor-bearing mice, intravital microscopy allowed the detection of angiogenically activated endothelium at cellular resolution with a small scanning window and limited penetration depth, while magnetic resonance imaging was used to visualize angiogenesis at anatomical resolution throughout the entire tumor. Fluorescence imaging allowed whole-body investigation of angiogenic activity. Using these quantum dots and the aforementioned imaging modalities, the angiogenic tumor vasculature was readily detected with the highest angiogenic activity occurring in the periphery of the tumor. This nanoparticle may be employed for multimodality imaging of a variety of diseases that are accompanied by activation of endothelial cells. Furthermore, the current technology might be developed for molecular imaging of other pathophysiological processes.

show abstract

Section: Resultsmentioning

confidence: 91%

Molecular imaging of tumor angiogenesis using αvβ3-integrin targeted multimodal quantum dots

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Pre-contrast images were acquired, and then a bolus of Gadolinium-diethylenetriaminepen-taacetic acid (Gd-DTPA) was administered using an automated syringe pump. Data were imported into MATLAB and custom software was developed to return parametric maps of K trans , v e , and k ep (= K trans / v e , the efflux constant) [36–38] from the voxel-based DCE-MRI analysis. (See Supplemental Information for more details on the DCE-MRI experimental methods).…”

Section: Methodsmentioning

confidence: 99%

Trastuzumab improves tumor perfusion and vascular delivery of cytotoxic therapy in a murine model of HER2+ breast cancer: preliminary results

Sorace

Quarles

Whisenant

et al. 2016

Breast Cancer Res Treat

View full text Add to dashboard Cite

To employ in vivo imaging and histological techniques to identify and quantify vascular changes early in the course of treatment with trastuzumab in a murine model of HER2+ breast cancer. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantitatively characterize vessel perfusion/permeability (via the parameter Ktrans) and the extravascular extracellular volume fraction (ve) in the BT474 mouse model of HER2+ breast cancer (N = 20) at baseline, day one, and day four following trastuzumab treatment (10 mg/kg). Additional cohorts of mice were used to quantify proliferation (Ki67), microvessel density (CD31), pericyte coverage (α-SMA) by immunohistochemistry (N = 44), and to quantify human VEGF-A expression (N = 29) throughout the course of therapy. Longitudinal assessment of combination doxorubicin ± trastuzumab (N = 42) tested the hypothesis that prior treatment with trastuzumab will increase the efficacy of subsequent doxorubicin therapy. Compared to control tumors, trastuzumab-treated tumors exhibited a significant increase in Ktrans (P = 0.035) on day four, indicating increased perfusion and/or vessel permeability and a simultaneous significant increase in ve (P = 0.01), indicating increased cell death. Immunohistochemical and ELISA analyses revealed that by day four the trastuzumab-treated tumors had a significant increase in vessel maturation index (i.e., the ratio of α-SMA to CD31 staining) compared to controls (P < 0.001) and a significant decrease in VEGF-A (P = 0.03). Additionally, trastuzumab dosing prior to doxorubicin improved the overall effectiveness of the therapies (P < 0.001). This study identifies and validates improved perfusion characteristics following trastuzumab therapy, resulting in an improvement in trastuzumab-doxorubicin combination therapy in a murine model of HER2+ breast cancer. This data suggests properties of vessel maturation. In particular, the use of DCE-MRI, a clinically available imaging method, following treatment with trastuzumab may provide an opportunity to optimize the scheduling and improve delivery of subsequent cytotoxic therapy.

show abstract

“…To investigate the differences between tumor rim, i.e., the region with the highest expected angiogenic activity, and core, the tumor rim was first defined as a f1-mm thick peripheral zone with the strongest R 1 enhancement, in accordance with the approach taken by others (28,29). Using this thickness, the difference between cNGR-labeled and unlabeled pQDs was maximal (Fig.…”

mentioning

confidence: 99%

Quantitative Molecular Magnetic Resonance Imaging of Tumor Angiogenesis Using cNGR-Labeled Paramagnetic Quantum Dots

et al. 2008

View full text Add to dashboard Cite

The objective of this study was to develop and apply cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (cNGR-pQDs) for the noninvasive assessment of tumor angiogenic activity using quantitative in vivo molecular magnetic resonance imaging (MRI). cNGR was previously shown to colocalize with CD13, an aminopeptidase that is highly overexpressed on angiogenic tumor endothelium. Because angiogenesis is important for tumor growth and metastatization, its in vivo detection and quantification may allow objective diagnosis of tumor status and evaluation of treatment response. I.v. injection of cNGR-pQDs in tumorbearing mice resulted in increased quantitative contrast, comprising increased longitudinal relaxation rate and decreased proton visibility, in the tumor rim but not in tumor core or muscle tissue. This showed that cNGR-pQDs allow in vivo quantification and accurate localization of angiogenic activity. MRI results were validated using ex vivo two-photon laser scanning microscopy (TPLSM), which showed that cNGR-pQDs were primarily located on the surface of tumor endothelial cells and to a lesser extent in the vessel lumen. In contrast, unlabeled pQDs were not or only sparsely detected with both MRI and TPLSM, supporting a high specificity of cNGR-pQDs for angiogenic tumor vasculature. [Cancer Res 2008;68(18):7676-83]

show abstract

Dynamic contrast-enhanced magnetic resonance imaging at 1.5 Tesla with gadopentetate dimeglumine to assess the angiostatic effects of anginex in mice

Cited by 31 publications

References 16 publications

Molecular imaging of tumor angiogenesis using αvβ3-integrin targeted multimodal quantum dots

Molecular imaging of tumor angiogenesis using αvβ3-integrin targeted multimodal quantum dots

Trastuzumab improves tumor perfusion and vascular delivery of cytotoxic therapy in a murine model of HER2+ breast cancer: preliminary results

Quantitative Molecular Magnetic Resonance Imaging of Tumor Angiogenesis Using cNGR-Labeled Paramagnetic Quantum Dots

Contact Info

Product

Resources

About