Quantitative assessment of hypoxia in melanoma xenografts by dynamic contrast-enhanced magnetic resonance imaging: intradermal versus intramuscular tumors.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been suggested to be a useful method for assessing the extent of hypoxia in tumors. In this study, we investigated whether differences in hypoxic fraction between tumors caused by the site of growth can be detected by DCE-MRI. MATERIALS AND METHODS: Intradermal and intramuscular A-07 tumors were subjected to DCE-MRI, histological analysis of microvascular characteristics, and measurement of hypoxic cell fractions using a radiobiological assay and a pimonidazole-based immunohistochemical assay. Parametric images of E·F (blood perfusion) and v(e) (extracellular volume fraction) were produced by pharmacokinetic analysis of the DCE-MRI series. RESULTS: The intramuscular tumors had 3-4-fold higher hypoxic fractions than the intradermal tumors, owing to a lower microvascular density. This difference in extent of hypoxia was not detectable in the parametric MR images. Most likely, larger vessel diameters compensated for the lower vessel density in the intramuscular tumors, resulting in E·F images that were similar to those of the intradermal tumors. CONCLUSION: Quantitative assessment of hypoxic fractions from parametric MR images may require tumor site-specific translational criteria.