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DOI: 10.1148/radiol.2482071421
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(Radiology 2008;248:561-570.)
© RSNA, 2008

Molecular Imaging

Imaging Hypoxia in Orthotopic Rat Liver Tumors with Iodine 124–labeled Iodoazomycin Galactopyranoside PET1

Christopher C. Riedl, MD, Peter Brader, MD, Pat B. Zanzonico, PhD, Yun Shin Chun, MD, Yanghee Woo, MD, Paramjeet Singh, MD, Sean Carlin, PhD, Bixiu Wen, MD, C. Clifton Ling, PhD, Hedvig Hricak, MD, and Yuman Fong, MD

1 From the Departments of Radiology (C.C.R., P.B., H.H.), Medical Physics (P.B.Z., S.C., B.W., C.C.L.), and Surgery (Y.S.C., Y.W., P.S., Y.F.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room C-278, New York, NY 10021. Received August 9, 2007; revision requested October 10; revision received January 4, 2008; final version accepted February 29. Supported in part by R25-CA096945-3 (C.C.R., P.B., H.H.) and RO1 CA75416 (Y.F.) from the National Institutes of Health. Address correspondence to H.H. (e-mail: muellnea{at}mskcc.org).

Purpose: 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 124I-IAZGP uptake with independent measures of hypoxia and to determine the optimal time after injection to depict hypoxia.

Materials and 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. 124I-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 124I-IAZGP throughout all tumors. The 124I-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.

Conclusion: Regions of high 124I-IAZGP uptake in orthotopic rat liver tumors are consistent with independent measures of hypoxia; visualization of hypoxia with 124I-IAZGP PET is optimal 6 hours after injection.

© RSNA, 2008