Evaluation of lymph node metastases: comparison of gadofluorine M-enhanced MRI and diffusion-weighted MRI in a rabbit VX2 rectal cancer model

Purpose:

To compare the diagnostic performance of a diffusion‐weighted imaging (DWI) dataset and a gadofluorine M‐enhanced imaging dataset for identifying lymph node (LN) metastases in a rabbit rectal cancer model.

Materials and Methods:

VX2 carcinomas were injected into the rectum of 26 rabbits. Four weeks later, T2‐weighted imaging (T2WI), pre‐T1WI, DWI, and post‐T1WI were performed. Two radiologists independently reviewed the DWI set (T2WI, pre‐T1WI, DWI) and the gadofluorine M set (T2WI, pre‐ and post‐T1WI) and recorded their confidence scores for LN metastasis on a per‐LN basis. Receiver operating characteristic (ROC) analysis was performed to compare the area under the ROC curve (A_z) of the two imaging sets. Histopathologic results were used as the reference standard.

Results:

The A_z and sensitivity of the gadofluorine M set were comparable to those of the DWI set (A_z, for reader 1, 0.849, 0.829, P = 0.571; for reader 2, 0.923, 0.876, P = 0.212; sensitivity, for reader 1, 97%, 97%; for reader 2, 97%, 92%, P = 0.304). The specificity of the former was greater than that of the latter (for reader 1, 65%, 53%, P = 0.0003; for reader 2, 81%, 68%, P = 0.01).

Conclusion:

Gadofluorine M‐enhanced images provided greater specificity than DWI for identifying LN metastases, whereas the A_z and sensitivity of the former were comparable to those of the latter. J. Magn. Reson. Imaging 2012;35:1179‐1186. © 2012 Wiley Periodicals, Inc.     

In vitro labeling of glioma cells with gadofluorine M enhances T1 visibility without affecting glioma cell growth or motility.

Gadofluorine is a novel macrocyclic, amphiphilic gadolinium-based contrast agent. We found that malignant glioma cells could be labeled in vitro using Gadofluorine without the need for transfection agents or any other additional means. Labeling with Gadofluorine enhanced the visualization of glioma cells in T(1)-weighted sequences, even if the cells had been cultured in medium without Gadofluorine over several days. The intracellular uptake of Gadofluorine was measured and the loss of relevant amounts of Gadofluorine into the cell culture medium was ruled out by MRI. Confocal laser fluorescence microscopy revealed Cy-5-labeled Gadofluorine in the perinuclear cytoplasmic region, but neither within the nucleus nor bound to the cell membrane. Adverse effects of cellular Gadofluorine uptake were ruled out by proliferation and migration assays. Finally, in vivo analyses provided good visibility of labeled glioma cells in T(1)-weighted sequences after intracerebral injection in mice for more than 2 weeks. We thus conclude that Gadofluorine can easily be used to label glioma cells in vitro without affecting glioma cell biology. Gadofluorine provides an interesting alternative for cellular labeling if iron oxide particles are incorporated insufficiently by target cells or if the vicinity of susceptibility artifacts prohibits the use of signal-decreasing contrast agents.