Imaging hypoxia in orthotopic rat liver tumors with iodine 124-labeled iodoazomycin galactopyranoside PET Journal Article
| Authors: | Riedl, C. C.; Brader, P.; Zanzonico, P. B.; Chun, Y. S; Woo, Y.; Singh, P.; Carlin, S.; Wen, B.; Ling, C. C.; Hricak, H.; Fong, Y. |
| Article Title: | Imaging hypoxia in orthotopic rat liver tumors with iodine 124-labeled iodoazomycin galactopyranoside PET |
| Abstract: | 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. |
| Keywords: | unclassified drug; mortality; liver cell carcinoma; nonhuman; carcinoma, hepatocellular; liver neoplasms; positron emission tomography; biological marker; animal cell; animal; metabolism; animals; animal tissue; oxygen; animal experiment; animal model; immunofluorescence; time; hypoxia; tissue section; correlation analysis; radioactive iodine; drug uptake; isotope labeling; iodine radioisotopes; liver tumor; rat; positron-emission tomography; scintiscanning; hoe 33342; iodine 124; pimonidazole; rats; nude rat; rats, nude; image processing, computer-assisted; image processing; anoxia; nitroimidazole derivative; autoradiography; nitroimidazoles; tissue oxygenation; 2 (2 nitro 1h imidazol 1 yl) n (2,2,3,3,3 pentafluoropropyl)acetamide; morris hepatoma; iodoazomycin galactopyranoside i 124; monosaccharides; iodinated azomycin galactopyranoside; monosaccharide |
| Journal Title: | Radiology |
| Volume: | 248 |
| Issue: | 2 |
| ISSN: | 0033-8419 |
| Publisher: | Radiological Society of North America, Inc. |
| Date Published: | 2008-08-01 |
| Start Page: | 561 |
| End Page: | 570 |
| Language: | English |
| DOI: | 10.1148/radiol.2482071421 |
| PUBMED: | 18641253 |
| PROVIDER: | scopus |
| PMCID: | PMC2797648 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 17 November 2011" - "CODEN: RADLA" - "Source: Scopus" |
