1,3-Bis-[7-(3-amino-2,4,6-triiodophenyl)-heptanoyl]-2-oleoyl glycerol (DHOG) is incorporated in an injectable lipid-in-water emulsion to be used as a contrast agent for the enhancement of x-ray computed tomography (CT) and micro-CT images of the bloodstream and liver in small animals (1-3). Micro-CT is widely used for imaging mice and rats and produces detailed images of bone material, but, with this technique, differentiation of soft tissue in the images is limited without the use of a contrast agent. Another limitation of micro-CT is the longer duration required to obtain a scan with most of the currently available instrumentation. Water-soluble contrast agents used for micro-CT are cleared from circulation during the time required to complete a scan (3). To overcome the limitations of water-based contrast agents used with the micro-CT instruments, DHOG was developed as a lipid-in-water emulsion (DHOG-LE) that mimics chylomicron remnants to enable its uptake by liver hepatocytes. The formulation designed for hepatobiliary imaging is referred to as DHOG-LC. A second formulation (DHOG-VC) contains a pegylated lipid in addition to the other lipid components of the DHOG-LC formulation. The increased retention time of DHOG-LE improved the visualization of abdominal organs by imaging at short intervals after injection. Use of the lipid-in-water emulsion contrast agent, particularly the DHOG-VC formulation, has also helped delineate the vascular structures in the animals.
The small particle size of the emulsion allows it to be taken up by hepatocytes in a receptor-mediated process (1). Apolipoprotein-E associates with the particle, and the complex binds to the hepatocyte receptor sites and enhances the liver image. Both the liver-selective and blood pool formulations of DHOG image the vascular system and the liver, but the time courses for visualization of the two systems differ (1, 2, 4). The selectivity and uptake by the liver is largely dependent on the physical parameters of the lipid emulsion. The timing of elimination from the liver appears to depend on the DHOG component because the various iodinated triglycerides have different clearance profiles (3). The pegylated lipid present in DHOG-VC is believed to physically block the apolipoprotein-E–binding hepatocyte receptor system, resulting in prolonged circulation in blood until the polyethylene glycol arms are cleaved from the molecule (2). Uptake by the liver is believed to occur by a mechanism similar to that seen with the liver-selective preparation after cleavage.
This chapter is a brief review of DHOG emulsions, which are iodinated contrast agents, for use only in small animals. The product is not approved for use in humans by the United States Food and Drug Administration or equivalent regulators in other countries.