Preparation, characterization, and evaluation of ioxilan carbonate particles for computed tomography contrast enhancement of liver
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1Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Rationale And Objectives:
To prepare and characterize a new particulate contrast medium, cyclic carbonate of ioxilan (IX-C) particles, as a macrophage imaging agent for computed tomography (CT) enhancement of the liver.
Methods:
Cyclic carbonate of ioxilan was synthesized from ioxilan, a nonionic water-soluble contrast agent. The IX-C particles prepared by a solvent extraction-evaporation method were characterized by size distribution, degradability, suspension stability, and median lethal dose. Pharmacokinetics of IX-C particles and their effectiveness in enhancing liver attenuation and in detecting hepatic tumors were evaluated using normal and VX2-tumor-bearing rabbits.
Results:
The IX-C particles were biodegradable, with ioxilan and carbon dioxide as the degradation products. The particles had an average size of 1 to 2 microns and were stable in saline suspension. The median lethal dose determined for IX-C particles was 2.6 and 3.1 g/kg body weight for female and male rabbits, respectively. A dose of 200 mg iodine/kg body weight caused an increase of 38 Hounsfield units in liver attenuation. In rabbit, hepatic clearance of the contrast medium occurred in 2 days. A tumor barely visible in precontrast scans could be detected after contrast injection.
Conclusions:
Development of particulate contrast medium from nonionic contrast agents represents a new approach. Ioxilan carbonate particles have suitable physicochemical properties that warrant further studies before clinical evaluation.