Tumor hypoxia imaging in orthotopic liver tumors and peritoneal metastasis: a comparative study featuring dynamic 18F-MISO and 124I-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, (124)I-iodoazomycin galactopyranoside ((124)I-IAZG) and (18)F-fluoromisonidazole ((18)F-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 (18)F-FMISO, followed on the next day (upon complete (18)F decay) by (124)I-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 (124)I-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 (18)F-FMISO signal increased in tumors over the 3-h time course of observation. In contrast, after the initial injection, the (124)I-IAZG signal slowly and continuously declined in the tumors. Nevertheless, the tumor-to-normal-tissue ratios of (124)I-IAZG increased, but more slowly than those of (18)F-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:

(18)F-FMISO localizes in the same intra-tumor regions as (124)I-IAZG. The contrast ratios (tumor/background) reach similar values for the two hypoxia tracers, but at later times for (124)I-IAZG than for (18)F-FMISO and, therefore, with poorer count statistics. As a consequence, the (18)F-FMISO images are of superior diagnostic image quality to the (124)I-IAZG images in the Morris hepatoma McA-R-7777 tumor model.

• Authors: Christopher C Riedl, Peter Brader, Pat Zanzonico, Vincent Reid, Yanghee Woo, Bixiu Wen, C Clifton Ling, Hedvig Hricak, Yuman Fong, John L Humm
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 35 Issue 1 Pg. 39-46 (Jan 2008) ISSN: 1619-7089 [Electronic] Germany
• PMID: 17786438 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Monosaccharides
• Nitroimidazoles
• iodinated azomycin galactopyranoside
• fluoromisonidazole
• Misonidazole

Topics

• Animals
• Disease Models, Animal
• Half-Life
• Hypoxia (diagnostic imaging, metabolism)
• Liver Neoplasms, Experimental (diagnostic imaging, pathology)
• Misonidazole (administration & dosage, analogs & derivatives, pharmacokinetics)
• Monosaccharides (administration & dosage, pharmacokinetics)
• Nitroimidazoles (administration & dosage, pharmacokinetics)
• Peritoneal Neoplasms (diagnostic imaging, secondary)
• Positron-Emission Tomography
• Rats
• Tissue Distribution