Imaging Efficacy of a Hepatocyte-Selective Polyiodinated Triglyceride for Contrast-Enhanced Computed Tomography

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Abstract
DHOG-LE is an injectable polyiodinated triglyceride lipid emulsion providing contrast enhancement of the liver in CT. Studies were conducted to characterize the imaging efficacy of various DHOG-LE formulations as a function of both the administered iodine dose and the formulation composition. Four DHOG-LE preparations consisting of either 10, 20, 25, or 30% (w/v) total lipid were administered to anesthetized female Sprague Dawley rats as single intravenous bolus doses of 50, 100, 150, and/or 300 mg I/kg (n = 3 to 6 rats/formulation and dose). A 25% triolein lipid emulsion prepared without iodine was administered as a vehicle control at the highest dose volume (n = 6). Liver enhancement was evaluated as a function of time (0 to 24 hours) after administration of contrast by analyzing regions of interest from sequential body scans. At all dose levels, liver enhancement was observed after injection of each DHOG-LE formulation. Regardless of formulation composition, similar enhancement of the liver was noted when administered at an equivalent iodine dose. Liver enhancement increased proportionately with increasing iodine dose. Mean peak intensities for 50, 100, 150, and 300 mg I/kg doses were 78 HU (42% above baseline), 101 HU (84% above baseline), 125 HU (127% above baseline), and 195 HU (255% above baseline), respectively. Liver time-intensity profiles exhibited rapid uptake, prolonged enhancement up to 3 hours, and complete clearance of the majority of the formulations tested by 24 hours. Time and duration of peak intensities were also directly related to iodine dose. In the animal model tested, DHOG-LE imaging efficacy was directly related to iodine dose and was independent of formulation composition. Thus, administration of DHOG-LE in highly concentrated lipid preparations minimized administered dose volume and resulted in appreciable liver enhancement, even at the lowest dose of 50 mg I/kg.