Magnetic resonance characterization of tumor microvessels in experimental breast tumors using a slow clearance blood pool contrast agent (carboxymethyldextran-A2-Gd-DOTA) with histopathological correlation

Abstract

Carboxymethyldextran (CMD)-A2-Gd-DOTA, a slow clearance blood pool contrast agent with a molecular weight of 52.1 kDa, designed to have intravascular residence for more than 1 h, was evaluated for its potential to characterize and differentiate the microvessels of malignant and benign breast tumors. Precontrast single-slice inversion-recovery snapshot FLASH and dynamic contrast-enhanced MRI using an axial T1-weighted three-dimensional spoiled gradient recalled sequence was performed in 30 Sprague-Dawley rats with chemically induced breast tumors. Endothelial transfer coefficient and fractional plasma volume of the breast tumors were estimated from MRI data acquired with CMD-A2-Gd-DOTA enhancement injected at a dose of 0.1 mmol Gd/kg body weight using a two-compartment bidirectional model of the tumor tissue. The correlation between MRI microvessel characteristics and histopathological tumor grade was determined using the Scarff-Bloom-Richardson method. Using CMD-A2-Gd-DOTA, no significant correlations were found between the MR-estimated endothelial transfer coefficient or plasma volumes with histological tumor grade. Analysis of CMD-A2-Gd-DOTA-enhanced MR kinetic data failed to demonstrate feasibility for the differentiation of benign from malignant tumors or for image-based tumor grading.

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

“…An optimal payload of 22 Gd-DOTA with mal-BSA (Gd-DOTA) 22 showed contrast effects comparable to albumin (Gd-DTPA) 30 , which is used as a standard to evaluate performances of novel intravascular agents. (79)(80)(81)(82) Though further studies are required to evaluate immunogenicity of the agent, the high specificity of mal-BSA (Gd-DOTA) n shows promise for reducing dosage of administration and toxicity compared to high dose nonspecific contrast agents currently employed in the clinic. Future work includes isolating the regional domains of maleylated BSA that afford targeting in order to circumvent immune responses that may be provoked by full length protein.…”

Quantitative diffusion-weighted MR imaging in the differential diagnosis of breast lesion

“…These limits have stimulated the progressive diffusion of magnetic resonance imaging (MRI) as a powerful tool for the detection, diagnosis and staging of breast cancer. In particular, contrast-enhanced MRI has high sensitivity for invasive cancer detection but it has a variable specificity [4][5][6][7][8][9][10]. In an effort to increase breast MRI specificity, diffusion-weighted MRI (DWI) could represent a potential resource.…”

Cluster analysis of quantitative parametric maps from DCE-MRI: application in evaluating heterogeneity of tumor response to antiangiogenic treatment

“…gadoteridol), whereas at pre-clinical level several contrast agents having different size and protein binding capability have been investigated, either at intermediate or high magnetic field (2-4.7T) [12][13][14][15]. Intermediate molecular weight (MW) and macromolecular CAs have been shown to be more sensitive to changes in vascular permeability upon antiangiogenic therapies in comparison to low molecular weight CAs thanks to their reduced extravasation in healthy tissues [12,16,17].…”