Персона: Завестовская, Ирина Николаевна
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Инженерно-физический институт биомедицины
Цель ИФИБ и стратегия развития – это подготовка высококвалифицированных кадров на базе передовых исследований и разработок новых перспективных методов и материалов в области инженерно-физической биомедицины. Занятие лидерских позиций в биомедицинских технологиях XXI века и внедрение их в образовательный процесс, что отвечает решению практикоориентированной задачи мирового уровня – диагностике и терапии на клеточном уровне социально-значимых заболеваний человека.
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Ирина Николаевна
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- ПубликацияОткрытый доступNuclear nanomedicine using Si nanoparticles as safe and effective carriers of 188 Re radionuclide for cancer therapy(2019) Tischenko, V. K.; Mikhailovskaya, A. A.; Popov, A. A.; Tselikov, G.; Petriev, V. M.; Deyev, S. M.; Timoshenko, V. Y.; Prasad, P. N.; Zavestovskaya, I. N.; Kabashin, A. V.; Деев, Сергей Михайлович; Тимошенко, Виктор Юрьевич; Завестовская, Ирина Николаевна; Кабашин, Андрей Викторович© 2019, The Author(s). Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188 Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188 Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188 Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188 Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.
- ПубликацияТолько метаданныеComplex Compounds of Rhenium-188 and Gallium-68 Radionuclides and Their Behavior in the Organism of Laboratory Animals(2019) Petriev, V. M.; Tishchenko, V. K.; Smoryzanova, O. A.; Zavestovskaya, I. N.; Postnov, A. A.; Завестовская, Ирина Николаевна© 2019, Allerton Press, Inc.This paper concerns the study of pharmacokinetic properties of rhenium-188 and gallium-68 bound to a ligand based on tetraphosphonic acid (188 Re,68 Ga-EDTMP). The pharmacokinetics of 188 Re,68 Ga-EDTMP is studied using outbred rats after intravenous injection of the preparation; the results are compared with the properties of 188 Re-EDTMP and 68 Ga-EDTMP. Rapid and selective activity accumulation in bone tissue is observed. The peak specific contents of 68 Ga and 188 Re in the femoral bone are 6.85%/g and 2.76%/g, respectively. Throughout the study, the activity of radionuclides in bone tissue was higher than in blood and most soft tissue organs. 188 Re,68 Ga-EDTMP was excreted via the urinary tract. Increased activity is recorded in the thyroid gland. Other organs and tissues are characterized by low contents of the preparation. After intravenous injection of 188 Re-EDTMP and 68 Ga-EDTMP, the activity of 188 Re and 68 Ga is lower in comparison with 188 Re,68 Ga-EDTMP. Thus,188 Re,68 Ga-EDTMP is a promising preparation for theranostics of bone metastases.
- ПубликацияТолько метаданныеEffect of Gallium Carrier in Ga-68-Ethylenediaminetetrakis (Methylene Phosphonic Acid) on its Behavior in Laboratory Animals(2019) Petriev, V. M.; Tishchenko, V. K.; Stepchenkova, E. D.; Zavestovskaya, I. N.; Завестовская, Ирина НиколаевнаThis paper concerns the study of the effect of the stable gallium carrier and its concentration on the biodistribution of a new osteotropic compound based on N,N,N ' N '-ethylenediaminetetrakis (methylene phosphonic acid) and gallium-68 (Ga-68-EDTMP). The studies are performed on intact Wistar rats. It is shown that the bone tissue activity increases as the carrier is added, whereas it decreases in internals and tissues. The carrier concentration has no significant effect on the Ga-68-EDTMP.
- ПубликацияОткрытый доступBiological evaluation of histidine and tryptophan labeled with gallium-68 as potential tumor imaging agents(2019) Tishchenko, V. K.; Mikhailovskaya, A. A.; Kuzenkova, K. A.; Kaprin, A. D.; Petriev, V. M.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© 2019 Published under licence by IOP Publishing Ltd. Radiolabeled with gallium-68 amino acids can be interesting and promising probes for tumor imaging using positron emission tomography (PET). Radiolabeled amino acids target the increased amino acid transport in cancer cells compared with normal tissues. In this study we labeled two amino acids histidine and tryptophan with 68 Ga, investigated its biodistribution in Wistar rats with subcutaneously transplanted cholangioma RS-1 by gamma counting and compared them with 68 GaCl 3 . The accumulation of 68 Ga-histidine in tumor tissue increased approximately 6 fold from 0.11±0.04 %ID/g at 5 min post injection (p.i.) to 0.67±0.07 %ID/g at 3 h p.i. The amount of 68 Ga-tryptophan in tumor was also risen 2.4 fold from 0.34±0.18 %ID/g to 0.80±0.06 %ID/g at 5 min and 3 h p.i., respectively. In contrast, the uptake of 68 GaCl 3 decreased throughout the study from 0.34±0.07 %ID/g to 0.13±0.04 %ID/g. The uptake and retention of 68 Ga-histidine and 68 Ga-tryptophan in non-target organs, except kidney and femur, were higher than those of 68 GaCl 3 . In conclusion, the obtained results suggest that 68 Ga-histidine and 68 Ga-tryptophan could serve as potential new PET tracers for tumor imaging.
- ПубликацияОткрытый доступBiodistribution ex vivo of 213 Bi-KHEDP - A promising boneseeking agent for targeted alpha therapy(2019) Tishchenko, V. K.; Stepchenkova, E. D.; Ivanov, S. A.; Kaprin, A. D.; Petriev, V. M.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© 2019 Published under licence by IOP Publishing Ltd. Alpha-emitters are increasingly used for targeted alpha therapy because of their emission of high linear energy transfer (LET) particles with a relative short path length. Bismuth-213 ( 213 Bi, T 1/2 = 46 min) is one of the most suitable radiation sources for medical applications. In the present work the biodistribution of 213 Bi-monopotassium salt of 1-hydroxyethylidene diphosphonic acid ( 213 Bi-KHEDP) in intact mice was studied. It was shown that bones uptake of 213 Bi-KHEDP were higher than in the most soft tissue organs throughout the study. The bone-to-soft tissue ratios for 213 Bi-KHEDP were higher than the corresponding data for 213 BiCl 5 . Among the soft tissue organs, only kidneys had a high uptake of Bi-KHEDP and free 213 Bi. In conclusion, 213 Bi-KHEDP had a strong and selective bone affinity, indicating that this complex could be useful to deliver alpha-particle radiation to primary bone cancer and skeletal metastases.
- ПубликацияОткрытый доступBiodistribution of 68Ga-DTPMP as a potential bone-seeking imaging agent in normal rats and rats with experimental model of bone callus(2020) Tishchenko, V. K.; Stepchenkova, E. D.; Fedorova, A. V.; Petriev, V. M.; Postnov, A. A.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© Published under licence by IOP Publishing Ltd.Bone metastases are common in advanced stages of various cancers. Positron emission tomography (PET) with radiotracers based on phosphonates and gallium-68 is a promising method of bone metastases detection. In this work a new complex based on diethylene triamine pentamethylene phosphonate (DTPMP) labeled with 68Ga was developed and its biodistribution in normal Wistar rats and rats with experimental model of bone callus was studied. The biodistribution studies in normal rats revealed high skeletal uptake of 68Ga-DTPMP (up to 1.45 %ID/g in femur) with rapid blood clearance and minimal uptake in any other major organs, except kidneys. In rats with experimental model of bone callus the accumulation of activity in bones and soft organs and tissues was slightly lower as compared with normal rats. The amount of 68Ga-DTPMP in femur with bone callus was higher than in non-lesion bones and reached 1.90 %ID/g at 2 h p.i. Therefore, 68Ga-DTPMP could be a promising radiotracer for bone tumors imaging and could be a valuable alternative to 18F-FDG and 18F-NaF for PET centers without an onsite cyclotron.
- ПубликацияТолько метаданныеBone-seeking radiopharmaceuticals based on phosphonic acids and 68Ga (review) Остеотропные радиофармацевтические препараты на основе фосфоновых кислот и 68Ga (обзор)(2020) Tishchenko, V. K.; Ivanov, S. A.; Kaprin, A. D.; Petriev, V. M.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© 2020 National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation. All rights reserved.Bone metastases cause severe bone pain, growing with solid tumor progression, and lead to significant decreasing patients quality of life. Nowadays positron emission tomography (PET) is the most informative method of radionuclide imaging. PET is highly sensitive non-invasive method of visualization of biochemical and molecular processes in the body. It enables to detect tumor lesions when structure changes are not determined or are not specific. Now radiopharmaceuticals based on 18F are available for bone metastases detection by PET. Their major disadvantage is cyclotron-based synthesis of 18F that limits the application of 18F-containing radiopharmaceuticals. During the last 15-17 years the interest in 68Ga has increased drastically around the world. 68Ga is the promising generator-based radionuclide with appropriate nuclear properties (Т1/2=68 min, β+=89%, E+ βmax=1,9 MeV) for radiosynthesis of a broad spectrum of radiopharmaceuticals. In this work nuclear-physical, chemical and biological properties of gallium-68 (68Ga) are presented. The approaches to synthesis of new bone-seeking compounds based on phosphonic acids and 68Ga are highlighted in detail. Thorough data about experimental studies and clinical application of the most promising compounds are also shown in this article.
- ПубликацияОткрытый доступEx vivo biodistribution of gallium-68-labeled porous silicon nanoparticles(2020) Tishchenko, V. K.; Mikhailovskaya, A. A.; Smoryzanova, O. A.; Petriev, V. M.; Kabashin, A. V.; Zavestovskaya, I. N.; Кабашин, Андрей Викторович; Завестовская, Ирина Николаевна© Published under licence by IOP Publishing Ltd.The introduction of nanotechnology in nuclear imaging has gained significant interest and could have promising potential for clinical use. Tumor imaging with radiolabeled nanoparticles (NPs) may be used for early detection, characterization, staging of disease, and for monitoring treatment efficacy. In this study we evaluated the biodistribution of porous silicon NPs labeled with positron-emitter gallium-68 in Wistar rats with subcutaneously transplanted cholangioma RS-1. The uptake of 68Ga-NPs in tumor tissue was 0.240.02 %ID/g at 5 min postinjection (p.i.) and climbed to 0.870.07 %ID/g at 5 h p.i. On the other hand, the amount of free 68Ga injected as 68GaCl3 solution decreased from 0.340.07 %ID/g at 5 min p.i. to 0.070.01 %ID/g at 5 h p.i. The highest level of radioactivity revealed in liver (8.27-15.79 %ID/g), spleen (0.98-1.27 %ID/g), and lungs (0.98-1.80 %ID/g). 68Ga-NPs were also determined in blood: up to 3.330.14 %ID/g at 5 min p.i. The uptake of 68Ga-NPs in other organs and tissues didn't exceed 1 %ID/g. In conclusion, the obtained results suggest that 68Ga-NPs could be suitable for use as molecular imaging probes.
- ПубликацияОткрытый доступThe influence of chemical structure of phosphonic acids labeled with gallium-68 on their pharmacokinetic properties in animals(2020) Tishchenko, V. K.; Mikhailovskaya, A. A.; Stepchenkova, E. D.; Kuzenkova, K. A.; Petriev, V. M.; Postnov, A. A.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© Published under licence by IOP Publishing Ltd.68 Ga-labeled phosphonates are of great interest due to their possibility to serve promising agents in nuclear medicine for bone tissue PET imaging. It is known that multidentate aminophosphonate ligands could form much stable chelates with different radiometals as compared to diphosphonates. In this work we studied the pharmacokinetic properties of 68Ga-labeled complexes with two, four and five phosphonate groups (68Ga-HEDP, 68Ga-EDTMP, and 68Ga-DTPMP, respectively) in normal Wistar rats after intravenous administration. It was shown that the structure of phosphonates had a great influence on the biodistribution of 68Ga-HEDP, 68Ga-EDTMP, and 68Ga-DTPMP. Complexes with higher number of aminomethylenephosphonate groups (68Ga-EDTMP and 68Ga-DTPMP) had higher bone uptake than diphosphonate 68Ga-HEDP. In blood 68Ga-HEDP had lower activity than 68Ga-EDTMP and 68Ga-DTPMP, indicating poor stability of diphosphonate-based complex. In other soft organs and tissues 68Ga-EDTMP and 68Ga-DTPMP uptake was slightly lower as compared with 68Ga-HEDP. In conclusion, 68Ga-EDTMP and 68Ga-DTPMP have the potential to be suitable radiotracers for bone tissue PET imaging.
- ПубликацияТолько метаданныеExperimental Study of the Biodistribution of New Bone-Seeking Compounds Based on Phosphonic Acids and Gallium-68(2020) Tishchenko, V. K.; Petriev, V. M.; Mikhailovskaya, A. A.; Stepchenkova, E. D.; Timoshenko, V. Y.; Postnov, A. A.; Zavestovskaya, I. N.; Тимошенко, Виктор Юрьевич; Завестовская, Ирина НиколаевнаWe investigate biodistribution of gallium-labeled hydroxyethylidenediphosphonic acid (Ga-68-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) (Ga-68-DTPMP) in intact Wistar rats. It was shown that Ga-68-DTPMP accumulated mainly in the bone tissue providing high femur/blood and femur/muscle ratios and had high stability in vivo. In contrast, Ga-68-HEDP was characterized by low stability and high uptake of radioactivity in blood throughout the study. So Ga-68-DTPMP can be considered as a new prospective radiotracer in oncology for imaging bone tissue metastasis by positron emission tomography.