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The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.
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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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PDF (RUS) Full-text article (in Russian)
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.