Dynamic contrast-enhanced magnetic resonance imaging in the assessment of early response to tumor necrosis factor alpha in a colon carcinoma model

OBJECTIVE: We describe the effects of tumor necrosis factor alpha (TNFalpha) on tumor microvasculature in a murine colon carcinoma model using serial dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). MATERIAL AND METHODS: Mice with subcutaneous murine colon carcinomas (MC-38) were imaged at 4.7 T after administration of 0.2 mmol/kg gadolinium-DTPA. Both treated and control mice (each group, n = 4), were scanned at baseline and 2, 4, 6, and 96 hours. A 2-compartment pharmacokinetic model generated parameters such as K, kep, and initial area under the gadolinium concentration curve (IAUC). RESULTS: The treatment group revealed significant differences in K at all time points after TNFalpha. kep and IAUC were significantly reduced at 2, 6, and 96 hours. The coefficient of variation in control animals ranged from 0.13 for IAUC to 0.30 for K. Mild histologic changes were observed at 2 to 6 hours, but considerable central necrosis with a vascular tumor rim was seen at 96 hours. CONCLUSION: DCE MRI can be used to detect early effects of TNFalpha. Serial DCE MRI is a promising tool in assessing the early effects of antivascular therapies.