Assessment of the hepatic tumor extracellular matrix using elastin-specific molecular magnetic resonance imaging in an experimental rabbit cancer model

Abstract

To investigate the imaging performance of an elastin-specific molecular magnetic resonance imaging (MRI) probe with respect to the extracellular matrix (ECM) in an experimental hepatic cancer model. Twelve rabbits with hepatic VX2 tumors were examined using 3 T MRI 14, 21, and 28 days after tumor implantation for two subsequent days (gadobutrol, day 1; elastin-specific probe, day 2). The relative enhancement (RE) of segmented tumor regions (central and margin) and the peritumoral matrix was calculated using pre-contrast and delayed-phase T1w sequences. MRI measurements were correlated to histopathology and element-specific and spatially resolved mass spectrometry (MS). Mixed-model analysis was performed to assess the performance of the elastin-specific probe. In comparison to gadobutrol, the elastin probe showed significantly stronger RE, which was pronounced in the tumor margin (day 14–28: P ≤ 0.007). In addition, the elastin probe was superior in discriminating between tumor regions (χ2(4) = 65.87; P < 0.001). MRI-based measurements of the elastin probe significantly correlated with the ex vivo elastinstain (R = .84; P <0 .001) and absolute gadolinium concentrations (ICP-MS: R = .73, P <0 .01). LA-ICP-MS imaging confirmed the colocalization of the elastin-specific probe with elastic fibers. Elastin-specific molecular MRI is superior to non-specific gadolinium-based contrast agents in imaging the ECM of hepatic tumors and the peritumoral tissue.

Visualization and Quantification of the Extracellular Matrix in Prostate Cancer Using an Elastin Specific Molecular Probe

“…An elastin-specific contrast agent has not only shown good results in cardiovascular diseases [ 42 , 43 , 44 ] but could also be used for the detection of malignant liver tumors. In a recent study, an elastin-specific contrast agent was used to visualize VX2-hepatic tumors in a rabbit model, and the use of the molecular agent to differentiate specific tumor and peritumoral regions based on its ECM composition was confirmed [ 31 ]. In addition, Sun et al were able to demonstrate the usefulness of the probe even in kidney fibrosis [ 45 ].…”

“…Finally, elastin represents a novel promising molecular biomarker also in the field of cardiovascular diseases [ 29 , 30 ]. Additionally, hepatic cancer [ 31 ] could be evaluated using an elastin-specific MRI molecular probe.…”

The extracellular matrix in hepatocellular carcinoma: Mechanisms and therapeutic vulnerability

“… 49 Elastin-based magnetic resonance imaging probes were implemented to detect ECM deposition in a rabbit HCC model. 50 Expectedly, EDPs can modulate tumor angiogenesis. 43 Despite these observations, how elastin responds to ECM crosslinking and stiffness are not clearly understood, as mouse models and human HCC studies analyzing the role of elastin are limited.…”