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.