Assessment of fraction of radiobiologically hypoxic cells in human melanoma xenografts by dynamic contrast‐enhanced MRI

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Abstract
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 × 0.6 × 2.0 mm3 with spoiled gradient‐recalled sequences. Images of E · F (E is the initial extraction fraction of Gd‐DTPA and F is perfusion) and λ (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 λ (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 λ 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. Magn Reson Med, 2006.