TY - JOUR
T1 - Dynamic contrast-enhanced magnetic resonance imaging in the assessment of early response to tumor necrosis factor alpha in a colon carcinoma model
AU - Tang, Jin Shan
AU - Choy, Garry
AU - Bernardo, Marcelino
AU - Thomasson, David
AU - Libutti, Steven K.
AU - Choyke, Peter L.
PY - 2006/9
Y1 - 2006/9
N2 - OBJECTIVE: We describe the effects of tumor necrosis factor alpha (TNFα) 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 TNFα. 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 TNFα. Serial DCE MRI is a promising tool in assessing the early effects of antivascular therapies.
AB - OBJECTIVE: We describe the effects of tumor necrosis factor alpha (TNFα) 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 TNFα. 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 TNFα. Serial DCE MRI is a promising tool in assessing the early effects of antivascular therapies.
KW - Angiogenic inhibitor
KW - Antivascular therapy TNFα
KW - Coefficients of variation
KW - DCE MRI
KW - General kinetic model
KW - Tumor
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U2 - 10.1097/01.rli.0000233882.83800.fb
DO - 10.1097/01.rli.0000233882.83800.fb
M3 - Article
C2 - 16896304
AN - SCOPUS:33747060166
SN - 0020-9996
VL - 41
SP - 691
EP - 696
JO - Investigative Radiology
JF - Investigative Radiology
IS - 9
ER -