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

Подъяблонский, А. С.; Белянин, М. Л.; Бородин, О. Ю.; Белоусов, Михаил Валерьевич; Brazovskii, Konstantin; Кривощеков, С. В.; Усов, В. Ю.; Шимановский, Н. Л.

doi:10.18705/2311-4495-2021-8-2-14-22

Cited by 3 publications

(5 citation statements)

References 9 publications

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“…Однако в последнее время удалось получить такое парамагнитное соединение с высокой степенью гепатотропности в эксперименте, как комплекс Mn-ДТПА-ГДОф [5], более чем на 70 % поглощаемое именно па-ренхимой печени и селезенки. Свойства марганца и технеция (и также -и рения) по их комплексообразующим свойствам, в частности с полиацетатными молекулами, достаточно близки, поскольку все они принадлежат к одной и той же -седьмой -группе менделеевской таблицы [6,7].…”

Section: Discussionunclassified

“…В ближайшее время будет завершено накопление и представлен материал по возможностям диагностического использования 99m Tc-ДТПА-ГДОф при различной патологии в эксперименте. В визуализации различных патологических состояний ДТПА-ГДОф высокоэффективен как парамагнитный контраст, будучи соединен с Mn(II) [5]. Вероятно его использование как гамма-излучателя с 99m Tc также окажется диагностически эффективным.…”

Section: Discussionunclassified

“…Учитывая склонность к формирвоанию коллоидных микрочастиц в водных растворах соединением ДТПА-ГДОф [4,5], будет представляет интерес и использование его в перспективе для сцинтиграфической визуализации лимфатической системы при нарушениях лимфодинамики и онкологических заболеваниях.…”

Section: Discussionunclassified

“…в последние годы удалось осуществить синтез такого гепатотропного гепатоселективного парамагнетика, как комплекс Mn(II) c 2-(2-карбоксиметил-(4-гекса-децилоксифенил-карбамоилметил)-аминоэтил)-аминоэтил-(4-гексадецил-оксифенил-карбамоилметил)-амино-уксусной кислотой (Mn-ДТПА-ГДОф) [4,5]. Было доказательно продемонстрировано высокое сродство молекулы ДТПА-ГДОф к паренхиме печени, в частности в форме парамагнетика Mn-ДТПА-ГДОф [5].…”

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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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Section: Discussionunclassified

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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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“…In addition, the use of Gd-CAs increases the cost of an expensive MR diagnostic. In this regard, the search for new CAs based on other low-cost substances, such as Mn, is in demand [26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Manganese-Doped Carbon Dots as a Promising Nanoprobe for Luminescent and Magnetic Resonance Imaging

Stepanidenko,

Vedernikova,

Badrieva

et al. 2023

Photonics

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Luminescent carbon nanodots (CDs) are a low-toxic nanomaterial with a tunable emission in a wide spectral range and with various functional groups on the surface. Therefore, CDs can prospectively serve as luminescent nanoprobes for biomedical applications, such as drug-delivery, visualization, sensing, etc. The doping of CDs with paramagnetic or transition metals allows the expansion of the range of applications of CDs and the fabrication of a multimodal nanoprobe for bioimaging. Here, we developed CDs doped with manganese (Mn) based on commonly used precursors—o-phenylenediamine or citric acid and formamide. The chemical structure, morphology, optical properties, and magnetic resonance responses have been carefully studied. The obtained CDs are up to 10 nm, with emissions observed in the 400–650 nm spectral region. CDs exhibit an ability to reduce both T1 and T2 relaxation times by up to 6.4% and 42.3%, respectively. The high relaxivity values suggest the use of CDs as promising dual-mode contrast agents for T1 and T2 MRI. Therefore, our developed CDs can be utilized as a new multifunctional nanoscale probe for photoluminescent and magnetic resonance bioimaging.

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Study of Organ Uptake of the New Hepatotropic Paramagnetic Contrast Agent, the Mn(II) Complex of 2-[2-Carboxymethyl-(4-Hexadecyloxyphenylcarbamoylmethyl)-Aminoethyl]-Aminoethyl-(4-Hexadecyloxyphenylcarbamoylmethyl)-Aminoacetic Acid (Mn-DTPA-GDOF), In Vivo in Some Experimental Models of Liver Damage in Rats

Belyanin,

Borodin,

Novozheeva

et al. 2024

Pharm Chem J

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

Cited by 3 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

Manganese-Doped Carbon Dots as a Promising Nanoprobe for Luminescent and Magnetic Resonance Imaging

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