Evaluation of manganese dimercaptosuccinate (mn-dmsa) complex as contrast agent for paramagnetic enhancement in mri studies of malignant fibroepithelial tumors in animals.

Ussov W. Yu., Belyanin M. L., Kovalenko A. Yu., Bezlepkin A. I., Filimonov V. D., Shimanovsky N.L.

Purpose. To develop a Mn-based paramagnetic contrast agent for imaging of tumor processes, employing avidity of dimercaptosuccinic acid (DMSA) to various neoproliferative structures, and for this aim we tested the paramagnetic complex Mn-DMSA in animals with fibrooseous nasal tumors. Materials and Methods. Complex Mn-DMSA was obtained using nanopowder tech-nology from manganese (II) carbonate and dimercaptosuccinic acid mixed together with ad-dition of trace amounts of water, and then dissolved in buffered saline, delivering finally the 0,5М solution of Mn-DMSA at pH=6,5. The Mn-DMSA was injected intravenously slowly to sleeping animals (7 cats and 2 dogs, all veterinary patients, with fibroepithelial nasopharin-geal tumors), as much as 0,05 ml of 0,5М solution per Kg of BW. MRI scanning in T1-weighted spin-echo mode has been carried out with TR = 500 ms and TE = 15 ms, in sagittal, axial and frontal slices as thin as 2-2,5 mm, to the matrix 256х256, with the field of view not larger than 200 х 200 mm. The uptake was reported visually as change in intensity of Т1-w MRI scans and quantitatively, with calculating for the Т1-w MRI images the index of enhancement (IE) of intensity per voxel, as : IE=(MeanInt of T1-w.MRI)Mn-DMSA / (MeanInt of T1-w.MRI)pre-contrast. Results. The R1 relaxivity of Mn-DMSA was obtained as 3,2 1/(s*mM). Visually on whole-body T1-w. SE scans the Mn-DMSA induced increase of intensity of the tumor, most prominent in the peripheral areas of tumor and less intense over the central non-perfused areas. The values of the IE were over 1,29 (IE=1,62 ± 0,12) for all peripheral parts of tumors , whereas only 1,23 ± 0,08 in central regiones. The normal musculoskeletal tissues did not enhance after Mn-DMSA injection, with IE = 1,07 ± 0,03. The uptake kblood-tissue constants were as little as < 0,12 ml/min/100 g for non-tumor tissues and over 0,24 ml/min/100 g in vascularised regions of tumors, with slow back diffusion and ktissue-blood < 0,04 ml/min/100 g. Conclusion. Paramagnetic complex Mn-DMSA provides obvious intense enhancement of musculoskeletal tumors in T1-SE MRI, demonstrates intermediate relaxivity R1, it is non-toxic and makes possible to image tumor processes in animals. The Mn-DMSA complex can be suggested as basic molecule for design of Mn paramagnetic agent for tumor imaging.

1 – Institute of Cardiology, Tomsk National research medical Center of the Russian Academy of Sciences. 2 – National research Tomsk Polytechnic University. 3 – Siberian state medical university. Tomsk, Russia. 4 – N.I. Pirogov Russian National research medical University, department of molecular pharmacology and radiobiology. Moscow, Russia.

 

 

 

 

 

Keywords:MRI, paramagnetic contrast enhancement, nasopharyngeal tumors, Mn-dimercaptosuccinate, Mn-DMSA.

 

Corresponding author:Ussov W. Yu., e-mail: Этот e-mail адрес защищен от спам-ботов, для его просмотра у Вас должен быть включен Javascript

 

For citation: Ussov W. Yu., Belyanin M. L., Kovalenko A. Yu., Bezlepkin A. I., Filimonov V. D., Shimanovsky N.L. Evaluation of manganese dimercaptosuccinate (mn-dmsa) complex as contrast agent for paramagnetic enhancement in mri studies of malignant fibroepithelial tumors in animals. REJR 2017; 7(4):108-116. DOI:10.21569/2222-7415-2017-7-4-108-116.

Received: 06.09.2017 Accepted: 20.11.2017