Synthesis, quantum chemistry analysis and pre-clinical in vivo evalution of magnetic resonance imaging abilities of paramagnetic manganese complex with 2,3-dimercaptosuccinate (succimang)

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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