Lipid-based blood-pool CT imaging of the liver

We have recently developed an iodinated lipid-based contrast agent capable of residing in the blood pool for extended periods of time relative to conventional water-soluble contrast agents. The purpose of this study was to examine the effects of combining this new blood-pool agent (ITG-PEG) with a hepatocyte-selective agent (ITG-LE; Molecular Biosystems) for accurate CT detection of small (< 10 mm) VX2 tumors in rabbit liver.

Preliminary pharmacokinetic analyses were conducted in SD rats (12) by injection of either I-125-labeled ITG-PEG or I-125-labeled ITG-LE followed by subsequent blood collection and quantification of radioactivity. Preliminary CT studies were conducted in both normal (3) and tumor-bearing NZW rabbits (2). Tumor-bearing rabbits were laparotomized and VX2 cells injected directly into the hepatic parenchyma to produce a total of eight focal lesions (2-10 mm diameter). Animals underwent CT scanning 10 days later with multiple techniques including noncontrast and helical i.v. enhanced (600 mg I/kg iohexol), and then 24 hours later using both ITG-PEG and ITG-LE (200 mg I/kg). Tissue density measurements (HU) of liver, tumor, and blood (descending aorta) were acquired in each case for comparison. Tumor morphology was verified by gross pathologic inspection.

Pharmacokinetic analysis in rats as well as CT studies in normal rabbits revealed that ITG-PEG remains in the blood-pool phase for more than 2 hours following i.v. administration. In fact, blood density in normal rabbit obtained with ITG-PEG was 95.1 HU +/- 5.8 at 120 minutes compared to 90.7 HU +/- 6.1 immediately after injection. Although liver enhancement was greater with iohexol (67 HU within 1 minute of injection), than for ITG-PEG/ITG-LE (32 HU, 60 minutes postinjection), liver to lesion ratios favored ITG-PEG/ITG-LE due to significant enhancement of tumor itself with iohexol (+40 HU). Tumor enhancement was minimal with ITG-PEG/ITG-LE. Lesions were subjectively much better defined with ITG-PEG/ITG-LE with sharper edge definition.

In these animal models, a new iodinated lipid-based contrast agent composed of both blood pool and hepatocyte-selective components afforded favorable CT imaging results compared to a conventional urographic agent, albeit at one-third the total iodine dose.