Document Detail

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?
MedLine Citation:
PMID:  19520288     Owner:  NLM     Status:  MEDLINE    
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.
Makiko Suehiro; Paul Burgman; Sean Carlin; Sean Burke; Guangbin Yang; Ouathek Ouerfelli; Christoph Oehler-Janne; Joseph O'Donoghue; Clifton Ling; John Humm
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-05-07
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  36     ISSN:  1872-9614     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-12     Completed Date:  2009-09-10     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  477-87     Citation Subset:  IM    
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
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MeSH Terms
Biological Markers / metabolism
Biological Transport / drug effects
Cell Hypoxia*
Cell Line, Tumor
Dose-Response Relationship, Drug
Galactosides / chemical synthesis*,  chemistry,  metabolism*,  pharmacokinetics
Nitroimidazoles / chemical synthesis*,  chemistry,  metabolism*,  pharmacokinetics
Oxygen / pharmacology
Substrate Specificity
Tissue Distribution
Grant Support
P01 CA115675-040001/CA/NCI NIH HHS; P01CA115675/CA/NCI NIH HHS; P30-CA 08748/CA/NCI NIH HHS
Reg. No./Substance:
0/1-(6-deoxy-6-iodogalactopyranosyl)-2-nitroimidazole; 0/Biological Markers; 0/Galactosides; 0/Nitroimidazoles; 7782-44-7/Oxygen

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