title: Imaging hypoxia in orthotopic rat liver tumors with iodine 124-labeled iodoazomycin galactopyranoside PET.
abstract: OBJECTIVE
  To evaluate iodine 124 (124I)-labeled iodoazomycin galactopyranoside (IAZGP) positron emission tomography (PET) in the detection of hypoxia in an orthotopic rat liver tumor model by comparing regions of high (124)I-IAZGP uptake with independent measures of hypoxia and to determine the optimal time after injection to depict hypoxia.
  
  
  METHODS
  The institutional animal care and use committee approved this study. Morris hepatoma tumors were established in the livers of 15 rats. Tumor oxygenation was measured in two rats with a fluorescence fiberoptic oxygen probe. (124)I-IAZGP was coadministered with the established hypoxia markers pimonidazole and EF5 in nine rats; 12-hour PET data acquisition was performed 24 hours later. Tumor cryosections were analyzed with immunofluorescence and autoradiography. In the four remaining rats, serial 20- and 60-minute PET data acquisition was peformed up to 48 hours after tracer administration.
  
  
  RESULTS
  Oxygen probe measurements showed severe hypoxia (<1 mm Hg) distributed evenly throughout tumor tissue. Analysis of cryosections showed diffuse homogeneous uptake of (124)I-IAZGP throughout all tumors. The (124)I-IAZGP distribution correlated positively with pimonidazole (r = 0.78) and EF5 (r = 0.76) distribution. Tracer uptake in tumors was detectable with PET after 24 hours in seven of nine rats. In rats that underwent serial PET, tumor-to-liver contrast was sufficient to enable detection of hypoxia between 6 and 48 hours after tracer administration. The optimal ratio between signal intensity and tumor-to-liver contrast occurred 6 hours after tracer administration.
  
  
  CONCLUSIONS
  Regions of high (124)I-IAZGP uptake in orthotopic rat liver tumors are consistent with independent measures of hypoxia; visualization of hypoxia with (124)I-IAZGP PET is optimal 6 hours after injection.
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room C-278, New York, NY 10021, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Riedl
authors.forename: Peter
authors.initials: P
authors.lastname: Brader
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: Yun Shin
authors.initials: YS
authors.lastname: Chun
authors.forename: Yanghee
authors.initials: Y
authors.lastname: Woo
authors.forename: Paramjeet
authors.initials: P
authors.lastname: Singh
authors.forename: Sean
authors.initials: S
authors.lastname: Carlin
authors.forename: Bixiu
authors.initials: B
authors.lastname: Wen
authors.forename: C Clifton
authors.initials: CC
authors.lastname: Ling
authors.forename: Hedvig
authors.initials: H
authors.lastname: Hricak
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000401:mortality; D000860:Hypoxia / Q000000981:diagnostic imaging; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D009005:Monosaccharides / Q000493:pharmacokinetics*; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D051381:Rats; D011923:Rats, Nude
chemical_list: D007457:Iodine Radioisotopes; D009005:Monosaccharides; D009593:Nitroimidazoles; C468007:iodinated azomycin galactopyranoside; C033815:pimonidazole