Preclinical Study of the Imaging Properties of the Mn(Ii)–D-Myo-Inositol-1, 2, 3, 4, 5, 6- Hexakisdihydrophosphoric Acid Complex as a Hepatospecific Paramagnetic Contrast Agent

Purpose: We tried to create a hepatospecific paramagnetic contrast agent – a paramagnetic analogue of 99mTc-technefit, by obtaining a paramagnetic Mn(II) complex with phytic (D-myo-inositol-1, 2, 3, 4, 5, 6– hexakisdihydrophosphoric) acid. Material and methods: A hepatotropic magnetic resonance contrast compound was obtained as an aqueous solution containing a paramagnetic Mn(II) complex with D-myo-inositol-1, 2, 3, 4, 5, 6-hexakis dihydrophosphoric (phytic) acid in a concentration of 0.5 M, with the addition of a 0.5M aqueous solution of meglumine (N-methylglucamine) in a ratio of 1:4 by volume to maintain pH in the range of 6.2–7.8, as well as to improve the stability of the solution. The working name of the Mn(II) complex with phytic acid phytomang®. The toxicological properties of the compound were evaluated when administered to laboratory mice, R1 relaxation and imaging properties in Wistar laboratory rats weighing 350-400 g, using low-field (field strength 0.2 T) and high-field (field strength 1.5 T) MR tomographs. Results: For 0.5 M of an aqueous solution of Mn-phytate, with the addition of meglumine, LD50, when administered acutely to laboratory animals – mice, is more than 18.7 ml / kg of body weight, which allows this compound to be classified according to GOST 12.1.007-76 standards to group 4 – low-hazard substances. The thermodynamic stability constant was 17.5. Spin-lattice relaxivity R1 in aqueous solution at a field strength of 0.2T: R1 = 6.82 1/ms. After intravenous administration to healthy rats with preserved liver function, Mn-phytate is distributed in the bloodstream, with rapid absorption within 5 minutes by liver tissue, followed by partial (up to 7 ± 3 % of the dose) excretion into bile after 30 minutes or more. The total uptake of the drug by the liver is 72 ± 7 % of the administered dose. Conclusion: The complex compound Mn (II) with D-myo-inositol-1, 2, 3, 4, 5, 6– hexakis dihydrophosphoric (phytic) acid belongs to low-toxic substances, is stable in aqueous media and has a high relaxability R1, selectively accumulates and intensively contrasts the liver parenchyma, and can be considered as the basis for creating a hepatospecific paramagnetic contrast preparation for use in MRI diagnostics liver in experimental and clinical studies.