Capillary leakage of a macromolecular MRI agent, carboxymethyldextran-Gd-DTPA, in the liver: Pharmacokinetics and imaging implications

Capillary leakage of a macromolecular contrast agent, Carboxymethyl Dextran-Gd-DTPA (CMD-Gd-DTPA) was characterized in a highly permeable system, the liver, to assess its potential as a blood pool marker. Its elimination kinetics in hepatic lymph were compared in nephrectomized rabbits with that of a tracer of extra cellular fluid space, Gd-DOTA. Four parameters were defined: volume of distribution, normalized initial leakage rate (ILRn), maximum ratio of lymph and plasma concentrations (max CLCP), and the time to obtain this maximum ratio. The effect of this leakage was studied on MR images by comparing liver contrast enhancement after injection and after almost total removal of the contrast agent from the blood by exchange transfusion. Capillary leakage of CMD-Gd-DTPA was detected in lymph. Compared to Gd-DOTA, it was slower (ILRn = 0.36 10−5 l min−1 for CMD-Gd-DTPA and ILRn = 2.6 10−5 l min−1 for Gd-DOTA), less abundant (max CLCP was 80% for CMD-Gd-DTPA and 100% for Gd-DOTA). Liver enhancement remained stable, which indicated that the leakage did not modify the enhancement induced by the intravascular fraction of the contrast agent. These results obtained in a highly permeable capillary model indicate that this agent can be used as a selective blood pool enhancer.