Abstract
Purpose: In this project, we developed novel methods to quantify changes in tumor hypoxia following a mild tempera-ture hyperthermia (MTH) treatment in rat HT29 human colon adenocarcinoma xenograft. Materials and Methods: An exogenous hypoxia marker (IAZGP) was labeled with two radioisotopes of iodine (131I and 123I, respectively) to form two distinct tracers. The two tracers were injected into HT29-bearing nude rats 4-hour before and immediately following 41.5℃, 45-minute mild hyperthermia treatment. The distributions of the two hypoxia tracers were obtained by performing digital autoradiography on tumor sections, and image processing resulted in quantitative information at 50 μm pixel size. Results: Following the hyperthermia treatment, there was a remarkable decrease in hypoxia tracer binding. The average whole tumor hypoxia tracer targeted fraction in five animals changed from 30.3% ± 9.7% to 13.0% ± 5.3% after the hyperthermia treatment (P = 0.001). Detailed pixelby-pixel analysis of the image data revealed a decline in hypoxia tracer uptake after hyperthermia in most regions. However, there was concomitant emergence of some new regions of hypoxia identified by increased tracer uptake. In the control group, the overall hypoxia tracer targeted fraction remained almost constant, with some hypoxic tracer redistribution (putative acute hypoxia) observed. Conclusion: Reoxygenation occurred in the rat HT29 xenograft following MTH treatment. This was evident with preponderance of decreased hypoxia specific tracer uptake on tumor sections. Our methodology might be a useful tool in hypoxia study.
Highlights
The hypoxia-related tumor microenvironments have become major targets of cancer treatment [1,2]
We proposed a novel approach of measuring tumor hypoxia changes with a single hypoxia tracer
The radiolabeled iodinated azomycin galactopyranoside (IAZGP) doses were prepared on the same day of the animal experiment
Summary
The hypoxia-related tumor microenvironments have become major targets of cancer treatment [1,2]. Applied mild temperature hyperthermia (MTH, 40.5 ̊C to 43 ̊C as per Urano et al [3]) has been tested for its efficacy to increase tumor oxygenation. Trimodality treatment with concurrent 41 ̊C, 60-minute hyperthermia, Taxol, and radiation was reported to increase partial oxygen tension (pO2) in locally advanced breast cancer [4]. In treatment studies of animal tumors, hyperthermia was shown to improve median pO2 and reduce hypoxic fraction (fraction of hypoxic tumor cells) in dogs with spontaneous soft tissue sarcomas [5]. Animal studies conducted by Song et al demonstrated that MTH alone might reduce tumor hypoxia in a variety of tumors [6]. In the reported animal studies, the hyperthermia temperature ranged from 38.5 ̊C to 43.5 ̊C, and the treatments lasted between 30 minutes to 2 hours [8].
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