medvisМедицинская визуализацияMedical Visualization1607-07632408-9516RDS-Media Ltd.10.24835/1607-0763-2019-3-133-143medvis-800Research ArticleНОВЫЕ ТЕХНОЛОГИИNEW TECHNOLOGIESПолучение, квантово-химический анализ и доклиническая in vivo оценка МРТ-визуализирующих свойств парамагнитного комплекса марганца с 2,3-димеркаптоянтарной кислотой (сукциманга)Synthesis, quantum chemistry analysis and pre-clinical in vivo evalution of magnetic resonance imaging abilities of paramagnetic manganese complex with 2,3-dimercaptosuccinate (succimang)УсовВ. Ю.UssovW. Yu.

доктор мед. наук, профессор, заведующий отделением рентгеновских и томографических методов диагностики

634012 Томск, Россия, ул. Киевская, 111

8-903-951-26-76

Doct. of med. sci., Professor, Head of X-ray and Tomographic Methods of Diagnosis

Kievskaya 111, 634012 Tomsk, Russia

Phone: +7-903-951-26-

ussov1962@yandex.ruФилимоновВ. Д.FilimonovV. D.

профессор, доктор хим. наук, профессор кафедры органической химии и биотехнологий

Томск

Doct. of chem. sci., Professor of the Department of Organic Chemistry and Biologically Active Substances

Tomsk

filimonov@tpu.ruБелянинМ. Л.BelyaninM. L.

канд. хим. наук, доцент, доцент кафедры органической химии и биотехнологий  

Томск

Cand. of chem. sci., Assistant Professor of Organic Chemistry and Biologically Active Substances Department

Tomsk

m_belyanin@mail.ruБезлепкинА. И.BezlepkinA. I.

директор 

Томск

Director

Tomsk

A_I_Bezlepkin@yandex.ruЛучичМ. А.LucicM. A.

профессор, доктор мед. наук, врач отделения МРТ 

Нови Сад

Doctor of Medicine, Professor

milos.a.lucic@gmail.comКоваленкоА. Ю.KovalenkoA. Yu.

аспирант отделения рентгеновских и томографических методов диагностики 

Томск

Postgraduate medical student of X-ray and Tomographic Methods of Diagnosis

Tomsk

nastenka13.06@mail.ruРоговскаяЮ. В.RogovskayaYu. V.

канд. мед. наук, заведующая отделением патоморфологии 

Томск

Cand. of med. sci., Head of the Department of Pathomorphology

Tomsk

rogovskaya@cardio-tomsk.ruШимановскийН. Л.ShimanovskiyN. L.

член-корр. РАН, доктор мед. наук, профессор, заведующий кафедрой молекулярной фармакологииимени академика П.В. Сергеева 

Москва

Corresponding Member of RAS, Doctor of Medicine, Professor, Head of the Department of acadecician P.V. Segeev Molecular Pharmacology, and Radiobilogy

Moscow

shimannn@yandex.ruНациональный исследовательский Томский политехнический университет, НИИ кардиологии Томского НИМЦ РАНРоссияNational Research Tomsk Polytechnic University, Research Institute of Cardiology of the Tomsk National Research Medical Center of the Russian Academy of SciencesRussian FederationНациональный исследовательский Томский политехнический университетРоссияNational Research Tomsk Polytechnic UniversityRussian FederationООО Ветеринарная клиника “Айболит”РоссияVetrinary research clinic “Aibolit” LtdRussian FederationЦентар за Имиджинг Диагностику, Институт у Сремской КаменициЧехословакияCenter of Imaging Diagnostic, Sremska KamenicaCzechoslovakiaНИИ кардиологии Томского НИМЦ РАНРоссияResearch Institute of Cardiology of the Tomsk National Research Medical Center of the Russian Academy of SciencesRussian FederationРоссийский Национальный исследовательский медицинский университет имени Н.И. ПироговаRussian Federation20190409201903133143Copyright © Усов В.Ю., Филимонов В.Д., Белянин М.Л., Безлепкин А.И., Лучич М.А., Коваленко А.Ю., Роговская Ю.В., Шимановский Н.Л., 20192019Усов В.Ю., Филимонов В.Д., Белянин М.Л., Безлепкин А.И., Лучич М.А., Коваленко А.Ю., Роговская Ю.В., Шимановский Н.Л.Ussov W.Y., Filimonov V.D., Belyanin M.L., Bezlepkin A.I., Lucic M.A., Kovalenko A.Y., Rogovskaya Y.V., Shimanovskiy N.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://medvis.rdsmedia.ru/jour/article/view/800Цель исследования

Цель исследования: осуществить синтез комплекса Mn(II) с димер каптоянтарной кислотой (ДМСА), средствами квантово-химического анализа оценить наиболее устойчивую структуру комплекса Mn с ДМСА и изучить накопление и контрастирующие свойства этого контраста-парамагнетика в структурах опухолевых и нормальных тканей у животных – ветеринарных пациентов (кошек с опухолями).

Материал и методы

Материал и методы. Синтез 2,3-димеркаптоянтарной кислоты (COOH-CHSH-CHSH-COOH) был осуществлен по модифицированной методике А.И. Бусева. По данным фантомных экспериментов определяли релаксивность R1. Визуализирующие возможности 0,5 М раствора Mn-(ДМСА)2 оценивали при МРТ в Т1-взвешенном спин-эхо режиме МРТ у животных – ветеринарных пациентов (кошек) с опухолями (ангиофибромы и фиброаденомы, 9 животных).

Результаты

Результаты. В результате квантово-химического анализа было установлено, что наиболее устойчивой является молекула комплекса Mn-(ДМСА)2. Релаксивность R1 комплекса Mn-(ДМСА)2 в водном растворе оказалась 3,2 1/(мМ•с), что соответствовало ранее полученным результатам. В норме Mn-(ДМСА)2 обеспечивает выраженное усиление паренхимы почек и умеренное – ткани печени, селезенки и тел позвонков. У животных с опухолями Mn-(ДМСА)2 выраженно усиливал Т1-взвешенное МРТ-изображение как периферических (индекс усиления = 1,87 ± 0,09, p < 0,01), так и центральных (индекс усиления = 1,59 ± 0,07, p < 0,01) отделов опухолей.

Заключение

Заключение. Визуализационные свойства Mn-(ДМСА)2 указывают на возможность создания на основе комплексов марганца парамагнитных контрастных препаратов, тропных к новообразованиям. Целесообразно дальнейшее исследование Mn-(ДМСА)2 для создания парамагнитного контрастного препарата.

Aim of the study. We have carried out the synthesis of complex of Manganese(II) with dimercaptosuccinic acid (DMSA), applied the quantum chemistry analysis for evaluation of most stable form of the Mn- DMSA complex and studied it’s uptake and imaging properties in normal and tumoral tissues in veterinary patients (cats with tumors)Material and methods. The synthesis of the 2.3-dimercaptosuccinic acid (COOH-CHSH-CHSH-COOH) has been carried out using modified technique proposed by A.I. Busev [Busev A.I. 1972]. Using phantoms filled in with 0.05 mM – 16 mM solutions of the agent we quantified the R1 relaxivity. Imaging properties of the 0.5 M solution of the Mn-(DMSA)2 were evaluated when performing the  contrastenhanced studies in veterinary patients (cats with adenofibrous tumors and angiofibromas, nine animals) using T1-w spin-echo mode.Results. As result of quantum chemistry analysis it was shown that the most stable complex of Mn(II) with DMSA is the molecule Mn-(DMSA)2. The R1 relaxivity of the Mn-(DMSA)2 complex in the water solution was as high as 3.2 1/(mM*s). In normal control animals the Mn-(DMSA)2 provided highly intensive enhancement of renal parenchyma and mild enhancement of liver, spleen and bone marrow. In animals with tumors the Mn-(DMSA)2 enhanced the T1-w spin-echo images of angiofibromas and fibroadenomas in both peripheral (index of enhancement = 1.87 ± 0.09, p < 0.01) and central (index of enhancement = 1.59 ± 0.07, p < 0.01) parts of the tumor.Conclusion. The imaging properties of the Mn-(DMSA)2 make an argue for real possibility of production of new non-Gadolinium paramagnetic contrast agents specific to tumors. Further study of the Mn-(DMSA)2 complex as paramagnetic contrast agent is of interest and useul.

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The authors declare that there are no conflicts of interest present.