Imaging hypoxia in orthotopic rat liver tumors with iodine 124-labeled iodoazomycin galactopyranoside PET.
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.
Riedl
Christopher C
CC
Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room C-278, New York, NY 10021, USA.
Brader
Peter
P
Zanzonico
Pat B
PB
Chun
Yun Shin
YS
Woo
Yanghee
Y
Singh
Paramjeet
P
Carlin
Sean
S
Wen
Bixiu
B
Ling
C Clifton
CC
Hricak
Hedvig
H
Fong
Yuman
Y
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
D007457:Iodine Radioisotopes; D009005:Monosaccharides; D009593:Nitroimidazoles; C468007:iodinated azomycin galactopyranoside; C033815:pimonidazole