Radioiodinated 1-(2-fluoro-4-iodo-2,4-dideoxy-beta-L-xylopyranosyl)-2-nitroimidazole: a novel probe for the noninvasive assessment of tumor hypoxia.

1-(2-Fluoro-4-iodo-2,4-dideoxy-beta-L-xylopyranosyl)-2-nitroimidazole (FIAZP) has been synthesized and labeled with radioiodine (125I). 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 [125I]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-beta-L-xylopranosyl)-2-nitroimidazo le 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.

Radioiodinated azomycin pyranoside (IAZP): a novel non-invasive marker for the assessment of tumor hypoxia.

1-(4-Iodo-4-deoxy-beta-L-xylopyranosyl)-2-nitroimidazole (Iodoazomycin Pyranoside; IAZP) was synthesized, labelled with radioiodine(123I, 125I) and evaluated for non-invasive assessment of tumor hypoxia. A biodistribution study with Balb/c mice bearing EMT-6 tumors showed a tumor-to-blood ratio of 13.9, representing 0.5 percent of injected dose per gram of tissue, at 24 hours post injection. This ratio is the highest for any 2-nitro-imidazole reported to date in this tumor model. Rapid elimination of radioactivity from the whole-body was noted (greater than 97% in 24 hours) and thyroid radioactivity at 24 hours was much lower than with other analogues of this series. No toxicity was observed in Balb/c mice at a dose 100 times higher than the anticipated human dose required for scintigraphic imaging. Planar, whole-body gamma scintigraphic images in the murine Balb/c EMT-6 tumor model clearly delineated tumor tissue at 24 hours post injection. These observations suggest that IAZP may be a suitable agent for non-invasive, clinical assessment of tumor hypoxia.