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).


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.


CONCLUSIONS
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.
Tang
Jin Shan
JS
Molecular Imaging Program, National Cancer Institute, NIH Building 10, Bethesda, MD 20892, USA.
Choy
Garry
G
Bernardo
Marcelino
M
Thomasson
David
D
Libutti
Steven K
SK
Choyke
Peter L
PL
D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D003287:Contrast Media; D004195:Disease Models, Animal; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D003287:Contrast Media; D014409:Tumor Necrosis Factor-alpha