Radioiodinated 1-(2-Fluoro-4-Iodo-2,4-Dideoxy-β-L-Xylopyranosyl)-2-Nitroimidazole: A Novel Probe for the Noninvasive Assessment of Tumor Hypoxia

1-(2-Fluoro-4-iodo-2,4-dideoxy-β-L-xylopyranosyl)-2-nitroimidazole (FIAZP) has been synthesized and labeled with radioiodine $({}^{125}{\rm I})$. Radioiodinated FIAZP is one of a series of sugar-coupled 2-nitroimidazoles developed in our laboratory as probes for noninvasive scintigraphic assessment of tumor Hypoxia. An in vivo biodistribution study with $[{}^{125}{\rm I}]{\rm FIAZP}$ in the murine BALB/c EMT-6 tumor model showed a tumor-to-blood ratio of 6, 24 h after injection, with 0.5% of the injected dose present per gram of tumor. These values are several times higher than the respective ratios and distribution values in any of the organs, with the exception of liver. Radioactivity from tissues other than tumor and liver declined with time, following the decline of blood radioactivity. Rapid whole-body elimination of radioactivity was observed (>96% in 24 h). The thyroid showed little uptake of radioactivity, indicating minimal in vivo deiodination. 1-(2-Fluoro-4-iodo-2,4-dideoxy-β-L-xylopranosyl)-2-nitroimidazole appears to undergo hypoxia-dependent binding in tumor tissue at levels comparable to those of other sugar-coupled 2-nitroimidazoles. The potential for imaging with this compound is discussed.