Assessment of tumor angiogenesis: dynamic contrast-enhanced MRI with paramagnetic nanoparticles compared with Gd-DTPA
Andrea Kassner1, Rebecca E Thornhill, Fang Liu
1Department of Medical Imaging, University of Toronto, Toronto, Canada. andrea.kassner@utoronto.ca
Abstract:
The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd-DTPA) using dynamic contrast-enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12-14 days after Vx-2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd-DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (K(i)) maps were calculated using a two-compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The K(i) values estimated using PNs were significantly lower than those obtained for Gd-DTPA (p = 0.018). When PNs and Gd-DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd-DTPA data (p = 0.34). The mean K(i) for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd-DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd-DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis.
Insights
Paramagnetic nanoparticles (PNs) show potential for characterizing tumor angiogenesis by revealing vascular permeability differences. Unlike Gd-DTPA, PNs highlight regional variations in tumor vasculature not detected by standard agents.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Oncology
Background:
- Tumor angiogenesis, the formation of new blood vessels, is crucial for tumor growth and metastasis.
- Characterizing tumor vasculature aids in treatment planning and monitoring.
- Current contrast agents may not fully capture the heterogeneity of tumor vascular permeability.
Purpose of the Study:
- To evaluate paramagnetic nanoparticles (PNs) as macromolecular MRI contrast agents for tumor angiogenesis.
- To compare the transendothelial transfer coefficient (K(i)) of PNs with Gd-DTPA in rabbit VX-2 tumors.
- To assess the ability of PNs to delineate regional differences in tumor vascular permeability.
Main Methods:
- Dynamic contrast-enhanced MRI (DCE MRI) was performed on rabbits with VX-2 tumors.
- Transendothelial transfer coefficient (K(i)) maps were calculated using a two-compartment model for both PNs and Gd-DTPA.
- Regions of interest were analyzed in the tumor core, rim, and hindlimb muscle.
Main Results:
- PNs showed significantly lower K(i) values compared to Gd-DTPA (p=0.018).
- PNs revealed significant differences in K(i) across tumor rim regions (p<0.0001), unlike Gd-DTPA (p=0.34).
- Tumor rim K(i) was significantly higher than tumor core or muscle for both agents.
Conclusions:
- Paramagnetic nanoparticles (PNs) demonstrate potential for noninvasive delineation of tumor angiogenesis.
- PNs can reveal regional vascular permeability differences in tumors missed by conventional agents like Gd-DTPA.
- PNs offer a promising tool for characterizing tumor vascular heterogeneity.
