THE ORETICAL BASIS AND EXPERIMENTAL STUDY OF COMPLEX OF MANGANESE (II) WITH HEXAMETHYL- PROPILENAMIN-OXIME AS PARAMAGNETIC CONTRAST AGENT FOR MR-IMAGING OF MALIGNANT TUMORS

Author:

Ussov W. Yu.1,Belyanin M. L.2,Filimonov V. D.2,Danilets M. G.3,Milto I. V.4,Vesnina Zh. V.5,Zorkaltsev M. A.4,Lucic M. A.6,Shimanovskiy N. L.7

Affiliation:

1. National Research Tomsk Polytechnic University; Research Institute of Cardiology of the Tomsk National Medical Research Center of the Russian Academy of Sciences

2. National Research Tomsk Polytechnic University

3. E. D. Goldberg Research Institute of pharmacology and regenerative medicine of the Tomsk National Medical Research Center of the Russian Academy of Sciences

4. Siberian State Medical University

5. Research Institute of Cardiology of the Tomsk National Medical Research Center of the Russian Academy of Sciences

6. Center of Diagnostic Imaging of the Institute of Oncology in Sremska Kamenica

7. National Research Moscow N. I. Pirogov Medical University

Abstract

Aim of the study. We attempted to obtain the Mn-HMPAO complex (Mangoxim) and to evaluate the possibility to apply as a paramagnetic contrast agent for enhancement of tumors at MRI. Materials and methods. The synthesis of HMPAO was carried out by using R. D. Neirinckx — J. Pijarowska-Kruszyna technique (2017), without separation of enantiomers. The Mn-HMPAO was obtained by mixing Manganese(II) carbonate with HMPAO, pH 6,2–6,5, 0,5 M. Also the quantum chemistry calculations were carried out on the structure of Mn-HMPAO using method of functional of density DFT rb3lyp/6–31+g(d,p) for isolated molecules and for water solutions (CPCM). MRI study of Mn-HMPAO uptake carried out in twelve laboratory mouses with transplanted Lewis sarcoma, in T1-w. SE mode, TR=500 ms, TE=15 ms, 256×256 matrix, FOV 15×15 cm, 3 mm thin slice. MRI acquired in 15–17 min and 60–90 min after intravenous injection of the Mn-HMPAO. The uptake was quantified as index of enhancement: IE=(Int. T1-w.MRI)Mn-HMPAO/(Int. T1- w.MRI)pre-contrast. Results. The N,N-Mn-dioxim is more stable than O,O-Mn-dioxim for 50,5 KCal/mol, so in the nature only N,N-Mn-dioxim exists. R1 of Mn-HMPAO was 3,35 1/(mM•s), below R1 of gadopentetate=3,96 1/(mM•s). The highest value of early IE was over the tumor (3,36±0,31) and over lungs (3,07±0,43). At 60 min the IE over tumor decreased to 1,58±0,14, remaining far over IE values over any other location. Conclusion. The Mn-HMPAO complex demonstrates paramagnetic properties for the application as the contrast MRI agent and probably will improve the selective enhancement of tumors.

Publisher

Baltic Medical Education Center

Subject

General Medicine

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