In vivo determination of tumor oxygenation during growth and in response to carbogen breathing using 15C5-loaded alginate capsules as fluorine-19 magnetic resonance imaging oxygen sensors.

Abstract

The objective was to present a method for the repeated noninvasive measurement of tumor oxygenation (Po(2)) over the whole period of tumor growth. A mixture of tumor homogenate (GH3 prolactinoma) and alginate capsules loaded with perfluoro-15-crown-5-ether (15C5) was injected into the flanks of Wistar Furth rats. The temporal behavior of tumor Po(2) was monitored between Day 1 and 26 after injection using fluorine-19 ((19)F) magnetic resonance imaging (MRI). In addition, the response of tumor Po(2) to modifiers of the tumor microenvironment (carbogen [95% O(2)/5% CO(2)], nicotinamide, and hydralazine) was investigated. An initial increase of tumor Po(2), probably reflecting neovascularization, followed by a decrease after Week 2, probably indicating tumor hypoxia or necrosis, were observed. The minimum and maximum average Po(2) +/- SEM observed were 3.3 +/- 2.0 mm Hg on Day 2 and 25.7 +/- 3.8 mm Hg on Day 13, respectively. Carbogen increased the tumor Po(2), whereas nicotinamide caused no significant change and hydralazine induced a significant decrease in tumor oxygenation. A preclinical method for the repeated noninvasive determination of tumor Po(2) was presented. It might help to investigate tumor physiology and the mechanisms of modifiers of the tumor microenvironment and their role in different therapeutic approaches.