Characterization and validation of noninvasive oxygen tension measurements in human glioma xenografts by 19F-MR relaxometry.

PURPOSE: The aim of this study was to characterize and to validate noninvasive 19F-magnetic resonance relaxometry for the measurement of oxygen tensions in human glioma xenografts in nude mice. The following three questions were addressed: 1. When perfluorocarbon compounds (PFCs) are administrated intravenously, which tumor regions are assessed by 19F-MR relaxometry? 2. Are oxygen tension as detected by 19F-MR relaxometry (pO2/relaxo) comparable to Eppendorf O2-electrode measurements (pO2/electrode)? 3. Can 19F-MR relaxometry be used to detect oxygen tension changes in tumor tissue during carbogen breathing? METHODS AND MATERIALS: Slice-selective 19F-MR relaxometry was carried out with perfluoro-15-crown-5-ether as oxygen sensor. The PFC was injected i.v. 3 days before the 19F-MR experiments. Two datasets were acquired before and two after the start of carbogen breathing. The distribution of PFCs and necrotic areas were analyzed in 19F-Spin Echo (SE) density MR images and T2-weighted 1H-SE MR images, respectively. One day after the MR investigations, oxygen tensions were measured by oxygen electrodes in the same slice along two perpendicular tracks. These measurements were followed by (immuno)histochemical analysis of the 2D distribution of perfused microvessels, hypoxic cells, necrotic areas, and macrophages.
RESULTS: The PFCs mainly became sequestered in perfused regions at the tumor periphery; thus, 19F-MR relaxometry probed mean oxygen tensions in these regions throughout the selected MR slice. In perfused regions of the tumor, mean PO2/relaxo values were comparable to mean PO2/electrode values, and varied from 0.03 to 9 mmHg. Median pO2/electrode values of both tracks were lower than mean pO2/relaxo values, because low pO2 electrode values that originate from hypoxic and necrotic areas were also included in calculations of median pO2/electrode values. After 8-min carbogen breathing, the average PO2/relaxo increase was 3.3 +/- 0.8 (SEM) mmHg and 2.1 +/- 0.6 (SEM) after 14 min breathing.
CONCLUSIONS: We have demonstrated that PFCs mainly became sequestered in perfused regions of the tumor. Here, mean PO2/relaxo values were comparable to mean PO2electrode values. In these areas, carbogen breathing was found to increase the PO2/relaxo values significantly.