Accurate prediction of
tumor metastatic potential would be helpful in treatment planning and in the design of agents that modify the
tumor phenotype. We report that three methods that are potentially transferable to the clinic--dynamic contrast enhanced MRI (DCE MRI), T(1rho)-weighted imaging and low temperature fluorescence imaging (that could be performed on biopsy specimens)--distinguished between relatively indolent (A375P) and aggressive (C8161) metastatic human
melanoma xenografts in nude mice, whereas T1 and T2 relaxation time measurements did not. DCE MRI data analyzed by the BOLus Enhanced Relaxation Overview (
BOLERO) method in conjunction with concurrent measurements of the arterial input function yielded a blood transfer rate constant (Ktrans) which measures perfusion/permeability, that was significantly higher in the core of the indolent
tumor than in the core of the aggressive
tumor. Histological staining indicated that aggressive
tumors had more blood vascular structure but fewer functional vascular structure than indolent
tumors. Indolent
tumors exhibited T(1rho), values that were significantly higher than those of aggressive
tumors at spin-locking frequencies >500 Hz. The mitochondrial redox ratio, Fp/(Fp+NADH), where Fp and
NADH are the fluorescence of oxidized
flavoproteins and reduced
pyridine nucleotides, respectively, of aggressive
tumors was much higher (more oxidized) than that of indolent
tumors and often showed a bimodal distribution with an oxidized core and a reduced rim. These differences observed between these two types of
tumors, one indolent and one aggressive, if generalizable, would be very valuable in predicting human
melanoma metastatic potential.