Abstract | INTRODUCTION: The hypoxia marker IAZGP, 1-(6-deoxy-6-iodo-beta-d-galactopyranosyl)-2-nitroimidazole, has been labeled with (123)I/(124)I/(125)I/(131)I via iodine-radioiodine exchange, which gives the radiotracer in a specific activity of 10-90 MBq/micromol. We synthesized the same radiotracer possessing several hundred to thousand times higher specific activity (high-SA IAZGP) via nucleophilic substitution and compared its biological behavior with that of conventionally produced IAZGP (low-SA IAZGP) to determine if specific activity is a factor influencing cell uptake kinetics, biodistribution and intratumor microregional localization of the radiotracer. METHODS: High-SA [(131)I]IAZGP was prepared by substitution of the tosyl functionality with [(131)I] iodide. In vitro uptake of high- and low-SA [(131)I]IAZGP by HCT8 and HT29 cells was assessed in normoxic and hypoxic conditions. Biodistribution and intratumor localization of high- and low-SA [(131)I]IAZGP were determined by injection into HT29 tumor-bearing mice. RESULTS: The nucleophilic substitution reaction proceeded efficiently in acetonitrile at 150 degrees C, giving the final product in an average yield of 42% and an average specific activity of 30 GBq/micromol. In vitro, high-SA [(131)I]IAZGP was incorporated into the tumor cells with similar kinetics and oxygen dependence to low-SA [(131)I]IAZGP. In HT29 tumor-bearing mice, biodistributions of high- and low-SA [(131)I]IAZGP were equivalent. Ex vivo autoradiography revealed heterogeneous intratumor localization of high-SA [(131)I]IAZGP corresponding closely to distributions of other exogenous and endogenous hypoxia markers. Comparable microregional distribution patterns were observed with low-SA [(131)I]IAZGP. CONCLUSIONS: Radiolabeled IAZGP produced via nucleophilic substitution is validated as an exogenous hypoxia marker. Specific activity does not appear to influence the in vivo hypoxia-mapping ability of the radiotracer.
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Authors | Makiko Suehiro, Paul Burgman, Sean Carlin, Sean Burke, Guangbin Yang, Ouathek Ouerfelli, Christoph Oehler-Janne, Joseph O'Donoghue, Clifton Ling, John Humm |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 36
Issue 5
Pg. 477-87
(Jul 2009)
ISSN: 1872-9614 [Electronic] United States |
PMID | 19520288
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- 1-(6-deoxy-6-iodogalactopyranosyl)-2-nitroimidazole
- Biomarkers
- Galactosides
- Nitroimidazoles
- Oxygen
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Topics |
- Animals
- Autoradiography
- Biological Transport
(drug effects)
- Biomarkers
(metabolism)
- Cell Hypoxia
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Galactosides
(chemical synthesis, chemistry, metabolism, pharmacokinetics)
- Humans
- Mice
- Nitroimidazoles
(chemical synthesis, chemistry, metabolism, pharmacokinetics)
- Oxygen
(pharmacology)
- Substrate Specificity
- Tissue Distribution
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