Paramagnetic contrast enhancement in MRI imaging of liver using an original hepatotropic high-affinity agent GDOF-Mn-DTPA

Abstract

Background. The use of modern hepatotropic contrast compounds is associated with the risk of side-effects, like accumulation of metal ions in tissues and the development of systemic pathological reactions. Therefore, currently, obtaining of high-affinity hepatotropic drugs is under investigation.Objective. There was studied the dependence of specific contrast properties of the paramagnetic complex 2-(2-carboxymethyl-(4-hexa-decyloxyphenyl-carbamoyl-methyl))-aminoethyl-(4-hexadecyl-oxyphenylcarbamoyl methyl)-aminoacetic acid with manganese — GDOF-Mn-DTPA — in magnetic resonance imaging from the administered dose of the drug. Design and methods. The dynamics of changes in the liver contrast ratio over time at different dosages of the contrast compound GDOF-Mn-DTPA was evaluated, and changes in the T1 relaxation time of liver and kidney tissue of laboratory animals (Wistar rats, more than 300 g) at different dosages of GDOF-Mn-DTPA were calculated.Results. Visual analysis of contrast-enhanced MRI scans with GDOF-Mn-DTPA already at a dose of 0.025 mmol/kg reliably visualized the accumulation of paramagnet in the liver, while further concentration of the drug in the bile ducts of animals was noted, with the actual absence of visually detectable kidney contrast. When evaluating the T1 relaxation time for the liver and kidneys, a persistent decrease in the T1 time for liver tissue was obtained for doses of 0.1, 0.05 and 0.025 mmol/kg, in particular for 0.025 mmol/kg from the initial 760 (747–755) MS to 488 (474–505) MS (p < 0.02). On the contrary, the obtained values of T1 relaxation time for kidney tissue showed no significant accumulation of the paramagnetic contrast compound GDOF-Mn-DTPA to the renal parenchyma at a dosage of 0.025 mmol / kg or lower. GDOF-Mn-DTPA showed a high degree of hepatoselectivity, with a pronounced reduced excretion through the kidneys.Conclusion. The GDOF-Mn-DTPA complex is a stable compound with a high degree of selective contrast of the hepatic parenchyma, with minimal or no renal excretion, a reliable basis for a hepatoselective contrast agent for imaging and functional studies of the liver with MRI and clinical use in the near future.