Liver contrast media for magnetic resonance imaging. Interrelations between pharmacokinetics and imaging

In the development of liver CM for MRI, three mainstream approaches have been undertaken: targeting of water-soluble MRI-CM to the hepatocytes, targeting of particles to the Kupffer cells of the liver, and application of macromolecular CM to tumorous tissue. As with the biliary iodinated CM, the physiological function of the liver has been used to target paramagnetic chelates (T1 agents) to the hepatocytes. Gd-EOB-DTPA and Gd-BOPTA are taken up mainly by hepatocytes and excreted into the bile by organic anion transporter (bilirubin transporter), whereas MnDPDP also uses the ability of hepatocytes to excrete metal ions, such as manganese. However, unlike the biliary iodinated CM, besides the specific accumulation in the hepatocytes, the low binding to plasma proteins and the high sensitivity of MRI, combined with the strong increase in relaxivity inside the hepatocellular environment, make the paramagnetic chelates very effective in the detection of liver lesions. Targeting of T2 agents (e.g. SPIO) to the Kupffer cells of the liver also has proved to be very effective in liver lesion detection. However, limited information is available regarding the pharmacokinetics of these particles in man and other problems, such as cardiovascular tolerance and manufacturing, must be overcome before widespread use of particulate CM can be implemented. The third approach is based on the differences in the vessel permeability, the vessel density, and functional lymphatics between normal and tumorous liver tissue when macromolecular CM are administered. This approach, however, is at an early research stage.