Radioiodinated 1-(5-iodo-5-deoxy-beta-D-arabinofuranosyl)-2-nitroimidazole (iodoazomycin arabinoside: IAZA): a novel marker of tissue hypoxia.
1-(5-Iodo-5-deoxy-beta-D-arabinofuranosyl)-2-nitroimidazole (IAZA) has been synthesised and labeled with 125I. Radioiodinated IAZA was shown to undergo hypoxia-dependent binding in EMT-6 cells in vitro and to have an initial binding rate of 284 pmole/10(6) cells/hr at a substrate concentration of 30 microM. This binding rate is more than three times that of the reference compound, misonidazole (89 pmole/10(6) cells/hr). The elevated binding rate was accompanied by in vitro cytotoxicity 30-40 times greater than that observed for misonidazole. Whole-body elimination and biodistribution studies in BALB/c mice bearing implanted, subcutaneous EMT-6 tumors showed a rapid excretion (greater than 98% in 24 hr) with moderate tissue levels which, in general, declined as a function of blood clearance. Tumor-to-blood ratios of 4.6 (4 hr) and 8.7 (8 hr), with respective tumor uptake values of 2.08% and 1.22% ID/g of tissue, form a rational basis for evaluation of this and related 2-nitroimidazole analogs as radiopharmaceuticals suitable for scintigraphic evaluation of tissue (tumor) hypoxia.
Mannan
R H
RH
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Somayaji
V V
VV
Lee
J
J
Mercer
J R
JR
Chapman
J D
JD
Wiebe
L I
LI
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000503:physiopathology; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D009593:Nitroimidazoles; C070588:iodoazomycin arabinoside