HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mannan, R. H. Articles by Wiebe, L. I. Search for Related Content PubMed PubMed Citation Articles by Mannan, R. H. Articles by Wiebe, L. I.

Radioiodinated 1-(5-Iodo-5-deoxy-ß-D-arabinofuranosyl)-2-nitroimidazole (Iodoazomycin Arabinoside: IAZA): A Novel Marker of Tissue Hypoxia

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, and Radiobiology Department, W. W. Cross Cancer Institute, Edmonton, Alberta, Canada

Correspondence: For reprints contact: John R. Mercer, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2N8.

ABSTRACT

1-(5-Iodo-5-deoxy-ß-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/10⁶ cells/hr at a substrate concentration of 30 µM. This binding rate is more than three times that of the reference compound, misonidazole (89 pmole/10⁶ 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 (>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.

This article has been cited by other articles:

				M. Piert, H.-J. Machulla, M. Picchio, G. Reischl, S. Ziegler, P. Kumar, H.-J. Wester, R. Beck, A. J.B. McEwan, L. I. Wiebe, et al. Hypoxia-Specific Tumor Imaging with 18F-Fluoroazomycin Arabinoside J. Nucl. Med., January 1, 2005; 46(1): 106 - 113. [Abstract] [Full Text] [PDF]

				T. Kaneta, Y. Takai, Y. Kagaya, Y. Yamane, H. Wada, M. Yuki, R. Iwata, M. Tsujitani, S. Takahashi, and S. Yamada Imaging of Ischemic but Viable Myocardium Using a New 18F-Labeled 2-Nitroimidazole Analog, 18F-FRP170 J. Nucl. Med., January 1, 2002; 43(1): 109 - 116. [Abstract] [Full Text] [PDF]

				T. Gronroos, O. Eskola, K. Lehtio, H. Minn, P. Marjamaki, J. Bergman, M. Haaparanta, S. Forsback, and O. Solin Pharmacokinetics of [18F]FETNIM: A Potential Hypoxia Marker for PET J. Nucl. Med., September 1, 2001; 42(9): 1397 - 1404. [Abstract] [Full Text] [PDF]

				D. Stypinski, S. A. McQuarrie, L. I. Wiebe, Y. K. Tam, J. R. Mercer, and A. J.B. McEwan Dosimetry Estimations for 123I-IAZA in Healthy Volunteers J. Nucl. Med., September 1, 2001; 42(9): 1418 - 1423. [Abstract] [Full Text] [PDF]

				Y.-Q. Li, J. R. Ballinger, R. A. Nordal, Z.-F. Su, and C. S. Wong Hypoxia in Radiation-induced Blood-Spinal Cord Barrier Breakdown Cancer Res., April 1, 2001; 61(8): 3348 - 3354. [Abstract] [Full Text]

				R. D. Okada, G. Johnson III, K. N. Nguyen, B. Edwards, C. M. Archer, and J. D. Kelly 99mTc-HL91 : Effects of Low Flow and Hypoxia on a New Ischemia-Avid Myocardial Imaging Agent Circulation, April 1, 1997; 95(7): 1892 - 1899. [Abstract] [Full Text]

				T. Bjornheden, M. Evaldsson, and O. Wiklund A Method for the Assessment of Hypoxia in the Arterial Wall, With Potential Application In Vivo Arterioscler. Thromb. Vasc. Biol., January 1, 1996; 16(1): 178 - 185. [Abstract] [Full Text]