Radiosynthesis of [(131)I]IAZGP via nucleophilic substitution and its biological evaluation as a hypoxia marker - is specific activity a factor influencing hypoxia-mapping ability of a hypoxia marker? Journal Article
| Authors: | Suehiro, M.; Burgman, P.; Carlin, S.; Burke, S.; Yang, G.; Ouerfelli, O.; Oehler-Janne, C.; O'Donoghue, J.; Ling, C.; Humm, J. |
| Article Title: | Radiosynthesis of [(131)I]IAZGP via nucleophilic substitution and its biological evaluation as a hypoxia marker - is specific activity a factor influencing hypoxia-mapping ability of a hypoxia marker? |
| Abstract: | Introduction: The hypoxia marker IAZGP, 1-(6-deoxy-6-iodo-β-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/μmol. 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°C, giving the final product in an average yield of 42% and an average specific activity of 30 GBq/μmol. 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. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; biological markers; mouse; animals; mice; tumor localization; oxygen; animal experiment; animal model; dose-response relationship, drug; molecular imaging; cell line, tumor; hypoxia; iodine 131; tissue distribution; substrate specificity; radioactivity; cell hypoxia; radiation dose distribution; biological transport; autoradiography; nitroimidazoles; iazgp; nucleophilic substitution; specific activity; 1 (6 deoxy 6 iodo beta dextro galactopyranosyl) 2 nitroimidazole i 131; galactosides |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 36 |
| Issue: | 5 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2009-07-01 |
| Start Page: | 477 |
| End Page: | 487 |
| Language: | English |
| DOI: | 10.1016/j.nucmedbio.2009.03.002 |
| PUBMED: | 19520288 |
| PROVIDER: | scopus |
| PMCID: | PMC2837594 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: NMBIE" - "Source: Scopus" |
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