Tumor hypoxia imaging in orthotopic liver tumors and peritoneal metastasis: A comparative study featuring dynamic (18)F-MISO and (124)I-IAZG PET in the same study cohort Journal Article


Authors: Riedl, C. C.; Brader, P.; Zanzonico, P.; Reid, V.; Woo, Y.; Wen, B.; Ling, C. C.; Hricak, H.; Fong, Y.; Humm, J. L.
Article Title: Tumor hypoxia imaging in orthotopic liver tumors and peritoneal metastasis: A comparative study featuring dynamic (18)F-MISO and (124)I-IAZG PET in the same study cohort
Abstract: Purpose: The purpose of this paper is to compare the uptake of two clinically promising positron emission tomography (PET) hypoxia targeting agents, 124I-iodoazomycin galactopyranoside (124I-IAZG) and 18F-fluoromisonidazole (18F-FMISO), by dynamic microPET imaging, in the same rats bearing liver tumors and peritoneal metastasis. Methods: Morris hepatoma (RH7777) fragments were surgically implanted into the livers of four nude rats. Tumors formed in the liver and disseminated into the peritoneal cavity. Each rat had a total of two to three liver tumors and peritoneal metastasis measuring 10-15 mm in size. Animals were injected with 18F-FMISO, followed on the next day (upon complete 18F decay) by 124I-IAZG. The animals were imaged in list mode on the microPET system from the time of injection of each tracer for 3 h and then again at 6 h and 24 h for the long-lived 124I-IAZG tracer (4.2-day half-life). Micro computed tomography (CT) scans of each rat were performed for co-registration with the microPET scans acquired with a liver contrast agent, allowing tumor identification. Regions of interest (ROIs) were drawn over the heart, liver, muscle, and the hottest areas of the tumors. Time-activity curves (TACs) were drawn for each tissue ROI. Results: The 18F-FMISO signal increased in tumors over the 3-h time course of observation. In contrast, after the initial injection, the 124I-IAZG signal slowly and continuously declined in the tumors. Nevertheless, the tumor-to-normal-tissue ratios of 124I-IAZG increased, but more slowly than those of 18F-FMISO and as a result of the differentially faster clearance from the surrounding normal tissues. These pharmacokinetic patterns were seen in all 11 tumors of the four animals. Conclusions: 18F-FMISO localizes in the same intra-tumor regions as 124I-IAZG. The contrast ratios (tumor/background) reach similar values for the two hypoxia tracers, but at later times for 124I-IAZG than for 18F-FMISO and, therefore, with poorer count statistics. As a consequence, the 18F-FMISO images are of superior diagnostic image quality to the 124I-IAZG images in the Morris hepatoma McA-R-7777 tumor model. © 2007 Springer-Verlag.
Keywords: controlled study; unclassified drug; nonhuman; comparative study; positron emission tomography; animals; computer assisted tomography; peritoneal neoplasms; tumor volume; animal experiment; animal model; hypoxia; imaging system; drug uptake; tissue distribution; liver tumor; rat; positron-emission tomography; 1 fluoro 3 (2 nitro 1 imidazolyl) 2 propanol f 18; rats; misonidazole; nude rat; tracer; drug half life; disease models, animal; peritoneum metastasis; anoxia; tumor diagnosis; nitroimidazoles; half-life; dynamic pet; micropet; fluoromisonidazole; iodoazomycin galactopyranoside; iodoazomycin galactopyranoside i 124; liver neoplasms, experimental; monosaccharides
Journal Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 35
Issue: 1
ISSN: 1619-7070
Publisher: Springer  
Date Published: 2008-01-01
Start Page: 39
End Page: 46
Language: English
DOI: 10.1007/s00259-007-0522-2
PUBMED: 17786438
PROVIDER: scopus
PMCID: PMC2723938
DOI/URL:
Notes: --- - "Cited By (since 1996): 14" - "Export Date: 17 November 2011" - "CODEN: EJNMA" - "Source: Scopus"
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MSK Authors
  1. Christopher Riedl
    60 Riedl
  2. Vincent J Reid
    9 Reid
  3. Bixiu Wen
    23 Wen
  4. Peter Brader
    25 Brader
  5. Yanghee Woo
    18 Woo
  6. Yuman Fong
    775 Fong
  7. Hedvig Hricak
    421 Hricak
  8. John Laurence Humm
    436 Humm
  9. Pat B Zanzonico
    357 Zanzonico
  10. C Clifton Ling
    331 Ling