Radioiodinated 1-(5-iodo-5-deoxy-beta-D-arabinofuranosyl)-2-nitroimidazole (iodoazomycin arabinoside: IAZA): a novel marker of tissue hypoxia.

Abstract

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.

• Authors: R H Mannan, V V Somayaji, J Lee, J R Mercer, J D Chapman, L I Wiebe
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 32 Issue 9 Pg. 1764-70 (Sep 1991) ISSN: 0161-5505 [Print] United States
• PMID: 1880579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Iodine Radioisotopes
• Nitroimidazoles
• iodoazomycin arabinoside

Topics

• Animals
• Cell Hypoxia (physiology)
• Iodine Radioisotopes
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Neoplasms, Experimental (metabolism, physiopathology)
• Nitroimidazoles (chemical synthesis, pharmacokinetics)
• Tissue Distribution