Study of Organ Uptake of the New Hepatotropic Paramagnetic Contrast Agent, the Mn(II) Complex of 2-[2-Carboxymethyl-(4-Hexadecyloxyphenylcarbamoylmethyl)-Aminoethyl]-Aminoethyl-(4-Hexadecyloxyphenylcarbamoylmethyl)-Aminoacetic Acid (Mn-DTPA-GDOF), In Vivo in Some Experimental Models of Liver Damage in Rats

• Published in: Pharmaceutical chemistry journal Vol. 58; no. 1; pp. 44 - 50
• Main Authors: Belyanin, M. L., Borodin, O. Yu, Novozheeva, T. P., Podyablonskiy, A. S., Belousov, M. V., Subbotina, O. A., Ussov, W. Yu, Shimanovskiy, N. L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2024
• Subjects: Medicine; Organic Chemistry; Pharmacology/Toxicology; Pharmacy; Mn-DTPA-GDOF; hepatotropic contrast agents; experimental hepatitis; MRI; paramagnetic contrast enhancement
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-024-03117-x

The results of studying magnetic resonance imaging (MRI) of rat liver performed with the original hepatotropic paramagnetic contrast agent (PMCA) Mn-DTPA-GDOF, the Mn(II) complex of 2-[2-carboxymethyl-(4-hexadecyloxyphenylcarbamoylmethyl)-aminoethyl]-aminoethyl-(4-hexadecyloxyphenylcarbamoylmethyl)aminoacetic acid, are presented. Mn-DTPA-GDOF was used as a colloidal solution (0.025 M, pH 8 – 9) with a free Mn(II) content <0.03% and a small excess of DTPA-GDOF (1 – 1.5%). Three groups of seven rats each with hepatitis, cholestatic cholangiohepatitis, and control intact animals were examined. The Mn-DTPA-GDOF accumulation dynamics in the liver were monitored on a Toshiba Vantage Titan 1.5 T MRI scanner. The contrast index was calculated as CI = I hep /I lim , where I hep is the contrast intensity of the liver and I lim , of the muscles of the lower limb. The CI of normal liver was 147 ± 5% and was reached by 20 min; with ligation of the common bile duct, CI = 125 ± 4% by 30 min; and with toxic hepatitis, CI = 112 ± 4% by 25 – 30 min. Toxic hepatitis was accompanied by extensive release of Mn-DTPA-GDOF into the intestine. Mn-DTPA-GDOF provided selective MRI contrast enhancement of liver parenchyma and could form the basis for developing a diagnostic clinical hepatotropic selective PMCA.