title: Detection of hypoxia in microscopic tumors using 131I-labeled iodo-azomycin galactopyranoside (131I-IAZGP) digital autoradiography.
abstract: OBJECTIVE
  Previous studies have shown that tumors less than 1 mm diameter derived from HT29 colorectal cancer cells are extremely hypoxic when grown intraperitoneally or intradermally in nude mice, whereas those of greater size (approximately 1-4 mm diameter) are not significantly hypoxic. The object of this study was to determine if digital autoradiography using the radiolabeled hypoxia imaging tracer iodo-azomycin galactopyranoside ((131)I-IAZGP) could detect hypoxia in this model.
  
  
  METHODS
  Microscopic HT29 tumors were grown as disseminated peritoneal disease and intradermally in nude mice. Tumors ranged in size from a few hundred microns to several millimeters in diameter. Animals were intravenously administered (131)I-IAZGP and pimonidazole 2 h before sacrifice. Following sacrifice, the intratumoral distribution of (131)I-IAZGP was assessed by digital autoradiography and compared with immunofluorescence microscopic images of pimonidazole binding and carbonic anhydrase IX (CAIX) expression.
  
  
  RESULTS
  The distributions of (131)I-IAZGP, pimonidazole, and CAIX expression were similar. Tumors less than 1 mm diameter displayed high (131)I-IAZGP uptake; these tumors also stained strongly for pimonidazole and CAIX. Larger tumors (approximately 1-4 mm diameter) were not significantly hypoxic and had low (131)I-IAZGP accumulation.
  
  
  CONCLUSIONS
  (131)I-IAZGP can detect hypoxia in microscopic tumors. Microscopic tumors are useful models for the validation of hypoxia radiotracers, and digital autoradiography is an appropriate technique for studying the distribution of hypoxia radiotracers in microscopic tumors.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. xiao-feng.li@louisville.edu
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Sun
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.forename: Makiko
authors.initials: M
authors.lastname: Suehiro
authors.forename: Mutian
authors.initials: M
authors.lastname: Zhang
authors.forename: James
authors.initials: J
authors.lastname: Russell
authors.forename: John L
authors.initials: JL
authors.lastname: Humm
authors.forename: C Clifton
authors.initials: CC
authors.lastname: Ling
authors.forename: Joseph A
authors.initials: JA
authors.lastname: O'Donoghue
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D001345:Autoradiography; D001692:Biological Transport; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D005697:Galactosides / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D009593:Nitroimidazoles / Q000378:metabolism; D011849:Radioactive Tracers; D011856:Radiographic Image Enhancement
chemical_list: C543418:1-(6-deoxy-6-iodogalactopyranosyl)-2-nitroimidazole; D000951:Antigens, Neoplasm; D005697:Galactosides; D009593:Nitroimidazoles; D011849:Radioactive Tracers; C033815:pimonidazole; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases