Detection of hypoxia in microscopic tumors using 131I-labeled iodo-azomycin galactopyranoside (131I-IAZGP) digital autoradiography
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Previous studies have shown that tumors less than 1 mm diameter derived from HT29 colorectal cancer cells are extremely hypoxic when grown intraperitoneally or intradermally in nude mice, whereas those of greater size (approximately 1–4 mm diameter) are not significantly hypoxic. The object of this study was to determine if digital autoradiography using the radiolabeled hypoxia imaging tracer iodo-azomycin galactopyranoside (131I-IAZGP) could detect hypoxia in this model.
Microscopic HT29 tumors were grown as disseminated peritoneal disease and intradermally in nude mice. Tumors ranged in size from a few hundred microns to several millimeters in diameter. Animals were intravenously administered 131I-IAZGP and pimonidazole 2 h before sacrifice. Following sacrifice, the intratumoral distribution of 131I-IAZGP was assessed by digital autoradiography and compared with immunofluorescence microscopic images of pimonidazole binding and carbonic anhydrase IX (CAIX) expression.
The distributions of 131I-IAZGP, pimonidazole, and CAIX expression were similar. Tumors less than 1 mm diameter displayed high 131I-IAZGP uptake; these tumors also stained strongly for pimonidazole and CAIX. Larger tumors (approximately 1–4 mm diameter) were not significantly hypoxic and had low 131I-IAZGP accumulation.
131I-IAZGP can detect hypoxia in microscopic tumors. Microscopic tumors are useful models for the validation of hypoxia radiotracers, and digital autoradiography is an appropriate technique for studying the distribution of hypoxia radiotracers in microscopic tumors.
KeywordsMicrometastasis Tumor hypoxia Iodo-azomycin galactopyranoside Hypoxia radiotracer Autoradiography
Grant support: National Institute of Health grants R01 CA84596 and P01 CA115675, National Cancer Institute grant P30-CA 08748.
Conflicts of interest
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