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

Purpose: The aim of this study was to characterize and to validate noninvas ive F-19-magnetic resonance relaxometry for the measurement of oxygen tensi ons 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)) compar able 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 du ring 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 a nd 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 investigati ons, oxygen tensions were measured by oxygen electrodes in the same slice a long two perpendicular tracks. These measurements were followed by (immuno) histochemical analysis of the 2D distribution of perfused microvessels, hyp oxic cells, necrotic areas, and macrophages. Results: The PFCs mainly became sequestered in perfused regions at the tumo r 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 track s were lower than mean pO(2/relaxo) values, because low pO(2/electrode) val ues that originate from hypoxic and necrotic areas were also included in ca lculations 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 pe rfused regions of the tumor. Here, mean pO(2/relaxo) values were comparable to mean pO(2/electrode) values. In these areas, carbogen breathing was fou nd to increase the pO(2/relaxo) values significantly. (C) 1999 Elsevier Sci ence Inc.