Medical Radiology and Radiation Safety. 2024. Vol. 69. № 6
DOI:10.33266/1024-6177-2024-69-6-56-63
W.Yu. Ussov1, M.L. Belyanin2, O.Y. Borodin3, A.I. Bezlepkin4, A.A. Churin5,
N.L. Shimanovsky6
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
1 E.N. Meshalkin National Medical Research Center, Novosibirsk, Russia
2 National Research Tomsk Polytechnic University, Tomsk, Russia
3 Tomsk Regional Oncological Dispensary, Tomsk, Russia
4 Aldan-Vet Veterinary Clinic LLC, Tomsk, Russia
5 E.D. Goldberg Institute of Pharmacology and Restorative Medicine, Tomsk, Russia
6 N.I. Pirogov Russian National Research Medical University, Moscow, Russia
Contact person: Wladimir Yuryevich Ussov, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. , This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
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.
Keywords: MRI, liver, paramagnetic contrast, Mn(II)-phytate, Phytomang, phytic acid, D-mio-inositol-1, 2, 3, 4, 5, 6-hexakisdihydrophosphoric acid, preclinical study
For citation: Ussov WYu, Belyanin ML, Borodin OY, Bezlepkin AI, Churin AA, Shimanovsky NL. 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. Medical Radiology and Radiation Safety. 2024;69(6):56–63. (In Russian). DOI:10.33266/1024-6177-2024-69-6-56-63
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Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.07.2024. Accepted for publication: 25.09.2024.