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 F-19-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 F-19-MR relaxometry? 2. Are oxygen tension as detected by F-19-MR relaxometry (pO(2/relaxo)) comparable to Eppendorf O-2-electrode measurements (pO(2/electrode))? 3. Can F-19-MR relaxometry be used to detect oxygen tension changes in tumor tissue during carbogen breathing? Methods and Materials: Slice-selective F-19-MR relaxometry was carried out with perfluoro-15-crown-5-ether as oxygen sensor. The PFC was injected i.v. 3 days before the F-19-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 F-19-Spin Echo (SE) density MR images and T-2-weighted H-1-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, F-19-MR relaxometry probed mean oxygen tensions in these regions throughout the selected MR slice. In perfused regions Of the tumor, mean pO(2/relaxo) values were comparable to mean pO(2/electrode) values, and varied from 0.03 to 9 mmHg. Median pO(2/electrode) values of both tracks were lower than mean pO(2/relaxo) values, because low pO(2/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 pO(2/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 pO(2/relaxo) values were comparable to mean pO(2/electrode) values. In these areas, carbogen breathing was found to increase the pO(2/relaxo) values significantly. (C) 1999 Elsevier Science Inc.