Assessment of fraction of radiobiologic ally hypoxic cells in human melanoma xenografts by dynamic contrast-enhanced MRI

A noninvasive method for assessment of the extent of hypoxia in experimental and human tumors is highly needed. In this study, the potential usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was investigated, using gadopentetate dimeglumine (Gd-DTPA) as contrast agent and A-07 human melanoma xenografts as tumor model. DCE-MRI was performed at a voxel size of 0.3 x 0.6 x 2.0 mm(3) with spoiled gradient-recalled sequences. Images of E (.) F (E is the initial extraction fraction of Gd-DTPA and F is perfusion) and lambda (the partition coefficient of Gd-DTPA, which is proportional to extracellular volume fraction) were obtained by Kety analysis of DCE-MRI data. The study was based on the hypothesis that hypoxic tissue would have low E (.) F (i.e., poor oxygen supply) and/or low lambda (i.e., high cell density and, hence, high oxygen consumption rate). Twenty-two tumors were first subjected to DCE-MRI and then to measurement of fraction of hypoxic cells, using a radiobiological assay. E (.) F was found to be strongly correlated to fraction of hypoxic cells (P < 0.000001), whereas significant correlation between lambda and fraction of hypoxic cells could not be detected. It is thus possible that E (.) F may be a useful parameter for the extent of hypoxia in experimental and human tumors with physiologic properties similar to those of A-07 tumors. This possibility warrants further studies involving experimental tumors of several lines, as well as human tumors.