contrast-agent-p792 and Colorectal-Neoplasms

In this study, T2*- relaxivity contrast imaging (RCI) is proposed for new contrast generation in MRI. The method produces images of relaxivities r*2,vasc and r*2,EES caused by susceptibility gradients across the vessel walls and cell membranes, respectively. The sensitivity to noise was assessed with a simulation study, and initial results are presented for five colorectal tumor xenografts in nude mice. Simulations show that the new relaxivity parameters are at least as accurate and precise as standard parameters such as plasma volume and interstitial volume. Mean values of both relaxivities were significantly different (r*2,vasc=10.9±2.9 mM(-1) s(-1) and r*2,EES=15.6±2.6 mM(-1) s(-1)). r*2,vasc (r=0.67) and r*2,EES (r=0.52) were weakly correlated with plasma volume and interstitial volume, respectively. Images of r*2,vasc and r*2,EES reveal a different tumor structure than plasma volume and interstitial volume maps. These results suggest that relaxivity contrast imaging is practically feasible and might offer supplementary information compared to dynamic contrast-enhanced-MRI.

Topics: Algorithms; Animals; Cell Line, Tumor; Colorectal Neoplasms; Computer Simulation; Contrast Media; Heterocyclic Compounds; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Mice; Mice, Nude; Models, Biological; Organometallic Compounds; Pilot Projects; Reproducibility of Results; Sensitivity and Specificity

To examine dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a macromolecular contrast agent (P792) to visualize effects of radiotherapy (RT) on microvascular leakage in a colorectal cancer model.. CC531 tumors were induced in WAG/Rij rats. DCE-MRI was performed before and 5 days after 5 x 5 Gy of RT and parametric maps generated of the endothelial transfer constant (K(trans)) and the fractional interstitial space (Ve) according to the Tofts model. Tissue pO2 mapping was performed in each tumor core and rim before and after RT. Microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and pimonidazole hypoxia staining were compared with a control group of tumor-bearing rats.. Mean K(trans) and v(e) were significantly reduced after RT in all tumor regions. Mean pO2 was 6.8 mm Hg before RT vs. 7.7 mm Hg after RT (p < 0.001) in the tumor rim and 3.5 mm Hg before RT vs. 4.4 mm Hg after RT (p < 0.001) in the tumor core. Mean MVD in the tumor rim was 10.4 in the RT treated group vs. 16.9 in the control group (p = 0.061). VEGF expression was significantly higher in RT-treated rats. After RT, no correlation was found between DCE-MRI parameters and histologic parameters. A correlation was seen after RT between pO2 and K(trans) (r = -0.57, p = 0.08) and between pO2 and v(e) (r = -0.65, p = 0.04).. Dynamic contrast-enhanced-MRI with P792 allows quantification of microvascular changes in this colorectal model. RT significantly reduces neovascular leakage and enhances tissue oxygenation and VEGF expression. After RT, DCE-MRI parameters are related to tumor pO2, but not to MVD or VEGF expression.

Topics: Animals; Capillary Permeability; Cell Hypoxia; Cell Line, Tumor; Colorectal Neoplasms; Contrast Media; Heterocyclic Compounds; Magnetic Resonance Imaging; Male; Microcirculation; Models, Animal; Nitroimidazoles; Organometallic Compounds; Oxygen; Partial Pressure; Radiation-Sensitizing Agents; Rats; Vascular Endothelial Growth Factor A