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.
Mannan
R H
RH
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Mercer
J R
JR
Wiebe
L I
LI
Somayaji
V V
VV
Chapman
J D
JD
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D015224:Dideoxynucleosides; D007457:Iodine Radioisotopes; D009593:Nitroimidazoles; C078964:1-(2-fluoro-4-iodo-2,4-dideoxyxylopyranosyl)-2-nitroimidazole