JOURNAL DESCRIPTION
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. № 5
DOI:10.33266/1024-6177-2024-69-5-95-103
W.Yu. Ussov1, M.L. Belyanin2, A.I. Bezlepkin3, O.Y. Borodin4,
S.M. Minin1, E. Kobelev1, Yu.B. Lishmanov2, A.M. Chernyavsky1,
N.L. Shimanovsky5
Preclinical Study of the Mn(II) Complex with Glucaric Acid
as an Oncotropic Paramagnetic Contrast Agent for MR Imaging of Malignant Tumors
1 E.N. Meshalkin National Medical Research Center, Novosibirsk, Russia
2 National Research Tomsk Polytechnic University, Tomsk, Russia
3 Aldan-Vet Veterinary Clinic LLC, Tomsk, Russia
4 Tomsk Regional Oncological Dispensary, Tomsk, Russia
5 N.I. Pirogov Russian National Research Medical University, Moscow, Russia
Contact person: W.Yu. 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.
Summary
Purpose: Since currently there are no selective drugs for paramagnetic contrast enhancement (PMC) in MRI in the oncology clinic as such, we tried to obtain a selective oncotropic paramagnetic contrast agent (PMCA) – Mn(II) manganese compound with glucaric acid (used in combination with 99mTc for breast cancer (breast cancer), and to evaluate on the basis of animal studies the possibility of using Mn(II)-glucarate (Glucaromang) as an oncotropic PMCA in breast cancer.
Material and methods: The synthesis of glucaric acid was carried out by a modified method by oxidation of D-glucose with strong nitric acid. A solution of D-glucaric acid was used to produce manganese glucarate by combining with manganese oxide or carbonate with an excess of glucarate in solution, since one manganese atom forms a complex with two glucaric acid molecules.
The injection solution of the obtained Mn(II)-glucarate was adjusted to pH = 6.4–7.2 and sterilized by microfiltration through Millipore filters with a pore size of 0.22 μm. The toxicity indices LD10, LD50, LD90 (ml/kg) were determined in laboratory white mice. An in vivo MRI study of the tumor accumulation of Mn(II)-glucarate was performed in veterinary patients – cats (n = 9) with diagnosed breast cancer, who underwent body MRI to clarify the diagnosis and assess the extent of breast cancer, and 4 cats with malignant tumors of the neck and submandibular region (salivary glands). Scanning was performed using Toshiba Titan Vantage (Canon Medical) and Magnetom Open (Siemens Medical), with subsequent processing by Radiant (https://www.radiantviewer.com ).
Results: In the injection solution of Mn(II)-glucarate 0.5 M, free manganese was absent in detectable amounts, the excess of glucaric acid (has an antineoproliferative effect) was up to 2–2.5 %. Osmolality 1550±39 mOsmol/(kg H2O), viscosity 2.85±0.15 MPa·s, at 37 °C. When stored for 6 months, there was no release of manganese from the complex. The thermodynamic stability constant was 17.6–17.9. For the injection drug «Mn(II)-glucarate, 0.5M, aqueous solution”, the mortality rates for single administration in mice were, respectively: LD10 = 6.8 ± 5.0 ml/kg, LD50=15.1 ± 4.7 ml/kg, LD90=37.5 ± 23.8 ml/kg . When administered Mn(II)-glucarate as laboratory mice and cats with breast cancer did not show significant changes in the blood pattern and any side effects. The drug accumulated intensively in the primary tumor and metastases. The index of enhancement for T1-WI was 1.78 ± 0.082 (p < 0.02) for the primary tumor and 1.49 ± 0.09 (p < 0.05) for lymphogenic metastases.
Conclusion: Mn-glucarate is an original paramagnetic contrast agent, highly stable, non-toxic, providing in vivo intensive MRI imaging of tumor structures, in particular in breast cancer.
Keywords: magnetic resonance imaging, paramagnetic contrast enhancement, Mn(II)-glucarate, Glucaromang, breast cancer, mice, cats
For citation: Ussov WYu, Belyanin ML, Bezlepkin AI, Borodin OY, Minin SM, Kobelev E, Lishmanov YuB, Chernyavsky AM, Shimanovsky NL. Preclinical Study of the Mn(II) Complex with Glucaric Acid as an Oncotropic Paramagnetic Contrast Agent for MR Imaging of Malignant Tumors. Medical Radiology and Radiation Safety. 2024;69(5):95–103. (In Russian). DOI:10.33266/1024-6177-2024-69-5-95-103
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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: 20.05.2024. Accepted for publication: 25.06.2024.