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

Ussov, W. Yu.; Филимонов, В. Д.; Belyanin, M. L.; Bezlepkin, A. I.; Lučić, Miloš; Коваленко, А. С.; Rogovskaya, Yu. V.; Shimanovskiy, N. L.

doi:10.24835/1607-0763-2019-3-133-143

Cited by 4 publications

(1 citation statement)

References 9 publications

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“…Ранее на примере других комплексонов, в частности таких, как гексаметилпропиленаминоксим-ГМПАО [6], диаминоциклогексан-тетрауксусная кислота -ДЦТА [7], димеркаптоянтарная кислота -ДМСА [8], нам удалось с позиций квантовой химии и практических исследований на животных in vivo показать принципиальную схожесть их комплексообразования с элементами -соседями по VII столбцу менделеевской таблицы химических элементов -марганцем (представляющим из себя один из сильнейших парамагнетиков, незначительно уступающим по релаксивности R1 только Gd) и технецием-99m (наиболее широко используемым радионуклидом в сцинтиграфии и ОфЭКТ).…”

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Synthesis and Preclinical Evaluation of Imaging Abilities of 99mТс-DTPA-GDOF as a New Original Russian Hepatotropic Agent for Scintigraphy and SPECT Studies

Belyanin¹,

Podyablonsky²,

Borodin³

et al. 2022

MEDICAL RADIOLOGY AND RADIATION SAFETY

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Purpose: Was to obtain a radiopharmaceutical (RPH) ‒ 99mTc bound with DTPA-GDOF (2-(2-carboxymethyl-(4-hexa-decyloxyphenyl-carbamoyl-methyl)-aminoethyl)-aminoethyl-(4-hexadecyl-oxyphenyl-carbamoyl methyl)-aminoacetic acid) and evaluate in an in vivo experiment on laboratory rats the possibility of using as hepatotropic RPH for scintigraphy and SPECT. Material and methods: The synthesis of DTPA-GDOF was carried out according to the original method of M.L. Belyanin e.a. at the N.M. Kizhner Center of TPU, by the interaction of 4-hexadecyloxyaniline with diethylenetriaminopentaacetic acid (d-DTPA) anhydride in dimethylformamide medium. Then 2 mg of GDOF-DTPA powder was mixed with 0.5 ml of 5 % sodium bicarbonate solution and heated to 100 oC until completely dissolved. 2 mg of tin dichloride powder were added to the solution, stirred and incubated at 25 oC for at least 20 minutes. The resulting solution was mixed with 99mTc eluate with an activity of 3 MBq and incubated for 10 min at 25 oC. Control of the labelling efficiency of 99mTc with DTPA-GDOF was carried out by chromatography on paper, according to the method of Zimmer and Pavel (1977). An in vivo study of the absorption kinetics of 99mTc-DTPA-GDOF was performed on male rats of the Wistar line (n = 12) 300–350 g. 99mTc-DTPA-GDOF at a dosage of 0.025 mmol/kg, 3 MBq was injected into the femoral vein. All scans are performed using the SPECT/CT Siemens Symbia T. Dynamic planar study included recording 4 sec/frame for the first two minutes, 128 × 128 pixels, and then up to 20 min – as 15 s/frame, followed by a SPECT/CT of the whole body. The value of the fraction of extraction (retention) of RPH in the liver was calculated. The values of the organ accumulation of RPH were determined as the organ fraction of uptake of the agent relative to the total dose administered to the animal Results. The labeling efficiency of DTPA-GDOF with 99mTc in fresh eluate of a standard molybdenum generator was in all cases more than 94 % (on average 95.6 ± 2.1 %, thus the proportion of free technetium was up to 4‒4.5 %). When storing 99mTc-DTPA-GDOF at room temperature on a shelf for up to 5 hours, the release of 99mTc-from the complex with DTPA-GDOF did not exceed 3.1 ± 0.3 %. The extraction fraction of 99mTc-DTPA-GDOF in the liver is as high as 0.78 ± 0.04. The fraction of the injected dose taken up by the liver is up to 70 % (68.9 ± 8.9). The quota of the spleen uptake is 14.1 ± 4.2 %. The level of accumulation of 99mTc-DTPA-GDOF in the liver was then maintained steadily without a significant decrease for up to 16‒18 hours. Conclusion: The 99mTc-DTPA-GDOF complex is a original RFP, with a high 99mTc labeling efficiency, long-lasting stability after labelling, and providing in vivo highly specific long-term imaging of the liver and spleen with gamma scintigraphy and SPECT.

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Synthesis and Preclinical Evaluation of Imaging Abilities of 99mТс-DTPA-GDOF as a New Original Russian Hepatotropic Agent for Scintigraphy and SPECT Studies

Belyanin¹,

Podyablonsky²,

Borodin³

et al. 2022

MEDICAL RADIOLOGY AND RADIATION SAFETY

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Frontier Molecular Orbital Energies as Descriptors for Prediction of Antiglycating Activity of N-Hydroxybenzoyl-Substituted Thymine and Uracil**

et al. 2021

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Paramagnetic contrast enhancement in MRI imaging of liver using an original hepatotropic high-affinity agent GDOF-Mn-DTPA

Подъяблонский

Белянин

Бородин

et al. 2021

Transl. med. (Print)

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Background. The use of modern hepatotropic contrast compounds is associated with the risk of side-effects, like accumulation of metal ions in tissues and the development of systemic pathological reactions. Therefore, currently, obtaining of high-affinity hepatotropic drugs is under investigation.Objective. There was studied the dependence of specific contrast properties of the paramagnetic complex 2-(2-carboxymethyl-(4-hexa-decyloxyphenyl-carbamoyl-methyl))-aminoethyl-(4-hexadecyl-oxyphenylcarbamoyl methyl)-aminoacetic acid with manganese — GDOF-Mn-DTPA — in magnetic resonance imaging from the administered dose of the drug. Design and methods. The dynamics of changes in the liver contrast ratio over time at different dosages of the contrast compound GDOF-Mn-DTPA was evaluated, and changes in the T1 relaxation time of liver and kidney tissue of laboratory animals (Wistar rats, more than 300 g) at different dosages of GDOF-Mn-DTPA were calculated.Results. Visual analysis of contrast-enhanced MRI scans with GDOF-Mn-DTPA already at a dose of 0.025 mmol/kg reliably visualized the accumulation of paramagnet in the liver, while further concentration of the drug in the bile ducts of animals was noted, with the actual absence of visually detectable kidney contrast. When evaluating the T1 relaxation time for the liver and kidneys, a persistent decrease in the T1 time for liver tissue was obtained for doses of 0.1, 0.05 and 0.025 mmol/kg, in particular for 0.025 mmol/kg from the initial 760 (747–755) MS to 488 (474–505) MS (p < 0.02). On the contrary, the obtained values of T1 relaxation time for kidney tissue showed no significant accumulation of the paramagnetic contrast compound GDOF-Mn-DTPA to the renal parenchyma at a dosage of 0.025 mmol / kg or lower. GDOF-Mn-DTPA showed a high degree of hepatoselectivity, with a pronounced reduced excretion through the kidneys.Conclusion. The GDOF-Mn-DTPA complex is a stable compound with a high degree of selective contrast of the hepatic parenchyma, with minimal or no renal excretion, a reliable basis for a hepatoselective contrast agent for imaging and functional studies of the liver with MRI and clinical use in the near future.

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

Cited by 4 publications

References 9 publications

Synthesis and Preclinical Evaluation of Imaging Abilities of 99mТс-DTPA-GDOF as a New Original Russian Hepatotropic Agent for Scintigraphy and SPECT Studies

Synthesis and Preclinical Evaluation of Imaging Abilities of 99mТс-DTPA-GDOF as a New Original Russian Hepatotropic Agent for Scintigraphy and SPECT Studies

Frontier Molecular Orbital Energies as Descriptors for Prediction of Antiglycating Activity of N-Hydroxybenzoyl-Substituted Thymine and Uracil**

Paramagnetic contrast enhancement in MRI imaging of liver using an original hepatotropic high-affinity agent GDOF-Mn-DTPA

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