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.
Mannan
R H
RH
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Mercer
J R
JR
Wiebe
L I
LI
Kumar
P
P
Somayaji
V V
VV
Chapman
J D
JD
D000818:Animals; D006027:Glycosides / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism*; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D006027:Glycosides; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C078486:iodoazomycin pyranoside