LIVER CONTRAST-MEDIA FOR MAGNETIC-RESONANCE-IMAGING - INTERRELATIONS BETWEEN PHARMACOKINETICS AND IMAGING

In the development of liver CM for MRI, three main stream approaches have been undertaken: targeting of wa-ter-soluble MRI-CM to the hepatocytes, targeting of particles to the Kupffer cells of the liver, and application ofmacromolecular CM to tumorous tissue. As with the biliaryiodinated CM, the physiological function of the liver hasbeen used to target paramagnetic chelates (T1 agents) to thehepatocytes. Gd-EOB-DTPA and Gd-BOPTA are taken upmainly by hepatocytes and excreted into the bile by organicanion transporter (bilirubin transporter), whereas MnDPDP also uses the ability of hepatocytes to excrete metal ions, such as manganese. However, unlike the biliary iodinatedCM, 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 hepato cellular environment, make the paramag-netic chelates very effective in the detection of liver lesions.Targeting of T2 agents (e.g. SPIO) to the Kupffer cells ofthe liver also has proved to be very effective in liver lesiondetection. However, limited information is available re-garding the pharmacokinetics of these particles in man andother problems, such as cardiovascular tolerance and man-ufacturing, must be overcome before widespread use ofparticulate CM can be implemented. The third approach isbased on the differences in the vessel permeability, the ves-sel density, and functional lymphatics between normal andtumorous liver tissue when macromolecular CM are admin-istered. This approach, however, is at an early research stage. © 1993, J.B. Lippincott Company.