Assessment of Fraction of Hypoxic Cells in Human Tumor Xenografts with Necrotic Regions by Dynamic Contrast-Enhanced MRI

Egeland, T. A. M., Gaustad, J-V., Benjaminsen, I. C., Hedalen, K., Mathiesen, B. and Rofstad, E. K. Assessment of Fraction of Hypoxic Cells in Human Tumor Xenografts with Necrotic Regions by Dynamic Contrast-Enhanced MRI. Radiat. Res. 169, 689–699 (2008). The potential usefulness of gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessing hypoxia in tumors with significant necrosis was investigated. Small (100–350 mm3) and large (500–1000 mm3) D-12 and U-25 tumors were subjected to DCE-MRI, measurement of the fraction of necrotic tissue, and measurement of the fraction of radiobiologically hypoxic cells. Images of E·F (E is the initial extraction fraction of Gd-DTPA and F is perfusion) and λ (λ is proportional to extracellular volume fraction) were produced by subjecting the DCE-MRI data to Kety analysis. Necrotic tissue could be identified in λ images but not in E·F images of the tumors. Most voxels in viable tissue showed λ values of 0.15–0.70, whereas the λ values of most voxels in necrotic tissue were either 0.70. The E·F and λ frequency distributions of the viable tissue, but not the E·F and λ frequency distributions of the whole tissue, were consistent with the observation that the four groups of tumors showed similar fractions of radiobiologically hypoxic cells. E·F and λ images may thus provide useful information on the extent of hypoxia in tumors provided that voxels in necrotic tumor regions are identified and excluded from the images.