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

Purpose

The objective was to present a method for the repeated noninvasive measurement of tumor oxygenation (Po₂) over the whole period of tumor growth.

Methods and materials

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 Po₂ was monitored between Day 1 and 26 after injection using fluorine-19 (¹⁹F) magnetic resonance imaging (MRI). In addition, the response of tumor Po₂ to modifiers of the tumor microenvironment (carbogen [95% O₂/5% CO₂], nicotinamide, and hydralazine) was investigated.

Results

An initial increase of tumor Po₂, probably reflecting neovascularization, followed by a decrease after Week 2, probably indicating tumor hypoxia or necrosis, were observed. The minimum and maximum average Po₂ ± 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 Po₂, whereas nicotinamide caused no significant change and hydralazine induced a significant decrease in tumor oxygenation.

Conclusions

A preclinical method for the repeated noninvasive determination of tumor Po₂ 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.

Keywords:  Tumor Po2 , ¹⁹F-MRI , Magnetic resonance imaging , Carbogen , Perfluorocarbon , Hypoxia