On the possibility of using hyaluronic acid in a composition with rhenium-188 for radiosynoviorthesis
https://doi.org/10.33380/2305-2066-2025-14-2-1966
Abstract
Introduction. Osteoarthritis is one of the most common joint diseases. The number of patients is growing rapidly and by 2050, the number of people in the world suffering from osteoarthritis is expected to exceed 1 billion. In a number of European countries, radiosynoviorthesis is used as a treatment. It is based on irradiation of the joint synovium with intra-articular administration of various radiopharmaceuticals containing β-emitting radionuclides.
Aim. Development of a radiopharmaceutical composition for radiosynoviorthesis based on rhenium-188 and hyaluronic acid as a particle stabilizer.
Materials and methods. Sodium perrhenate solution, 188Re was obtained from a 188W/188Re generator "GREN-1" (JSC "SSC RF – IPPE", Russia). Eluate activity was measured on an ISOMED 2010 (PTW-Freiburg, Germany). Radiochemical purity was determined by thin-layer chromatography on thin-layer silica gel plates on aluminum substrate in acetone. The activity of chromatogram was measured on a Scan-RAM chromatogram scanner (LabLogic Systems Ltd., United Kingdom). pH was measured on S20 Seven Easy pH meter (METTLER TOLEDO, Switzerland). Particle size was determined by laser diffraction on an LA-350 device with a detection range of 0.1–1000 μm (HORIBA, Japan). Accumulation in the joint was determined on a Wizard 2480 gamma counter (PerkinElmer, USA) after intra-articular administration of the composition to mature conventional albino rats (females).
Results and discussion. The study included a comparison of the physic-chemical properties of the synthesized compositions with different volume activities, the optimal concentration of hyaluronic acid, and the methods for obtaining the radiopharmaceutical composition both from the liquid and freeze-dried reagents. The biological behavior of the radiopharmaceutical composition after intra-articular administration to mature conventional albino rats (females) were studied.
Conclusion. Radiopharmaceutical composition containing rhenium-188, tin dichloride and hyaluronic acid with a radiochemical purity of more than 95 % has been developed. The accumulation of the composition in the knee joint was more than 96 % 3 hours after intra-articular administration. This composition is of interest for further study as a radiopharmaceutical for radiosynoviorthesis.
Keywords
About the Authors
K. V. MayorovRussian Federation
8/1, Tvardovskogo str., Moscow, 123458
N. D. Beloglazova
Russian Federation
8/1, Tvardovskogo str., Moscow, 123458
N. G. Sashova
Russian Federation
8/1, Tvardovskogo str., Moscow, 123458
G. E. Kodina
Russian Federation
46, Zhivopisnaya str., Moscow, 123098
A. O. Malysheva
Russian Federation
46, Zhivopisnaya str., Moscow, 123098
O. E. Klementyeva
Russian Federation
23, Kashirskoe shosse, Moscow, 115522
References
1. Gill T. K., Mittinty M. M., March L. M., et al. Global, regional, and national burden of other musculoskeletal disorders, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. The Lancet Rheumatology. 2023;5(11):e670–e682. DOI: 10.1016/S2665-9913(23)00232-1.
2. Erdes S. F., Folomeeva O. M. Rheumatic diseases and disability of Russian Federation adult population. Rheumatology Science and Practice. 2007;45(4):4–9. (In Russ.) DOI: 10.14412/1995-4484-2007-4-9.
3. Nasonova E. L., editor. Russian clinical guidelines. Rheumatology. Moscow: GEOTAR-Media; 2017. 464 p. (In Russ.)
4. Cooper C., Dennison E., Edwards M. H. Epidemiology of ostheoarthritis. Medicographia. 2013;35(2):145–151.
5. Kampen W. U., Boddenberg-Pätzold B., Fischer M., Gabriel M., Klett R., Konijnenberg M., Kresnik E., Lellouche H., Paycha F., Terslev L., Turkmen C., van der Zant F., Antunovic L., Panagiotidis E., Gnanasegaran G., Kuwert T., van den Wyngaert T. The EANM guideline for radiosynoviorthesis. European Journal of Nuclear Medicine and Molecular Imaging. 2022;49:681–708. DOI: 10.1007/s00259-021-05541-7.
6. Drozdovsky B. Ya., Ikonnikov A. I., Krylov V. V. Radiosynoviorthesis in the treatment of patients with rheumatoid arthritis. Meditsinskaya radiologiya. 1990;35(7):6–9. (In Russ.)
7. Zverev A. V., Krylov V. V., Khanov A. G., Kochetova T. Yu. Radiosynovectomy – a method of inflammatory joints diseases treatment with the use of isotopes. RMJ. Medical Review. 2017;1(1):36–41. (In Russ.)
8. Kodina G. E., Malysheva A. O., Klementyeva O. Е., Taratonenkova N. A., Lyamtseva E. A., Zhukova M. V., Krasnoperova A. S. «Synoren, <sup>188</sup>Re» – a promising radiopharmaceutical for radiosynovectomy. Radiation and Risk. 2018;27(4):76–86. (In Russ.) DOI: 10.21870/0131-3878-2018-27-4-76-86.
9. Shamim S. A., Arora G., Jha P., Gupta P., Behera A., Mukherjee A., Prabhu M., Ansari M. T., Vyas S., Bal C. Comparison of Lutetium-177 tin colloid and Rhenium-188 tin colloid radiosynovectomy in chronic knee arthritis. Nuclear Medicine Communications. 2020;41(8):721–726. DOI: 10.1097/MNM.0000000000001210.
10. Production, quality control and clinical applications of radiosynovectomy agents. Vienna: International Atomic Energy Agency; 2021. 140 p.
11. Tsivadze A. Yu., Filyanin A. T., Romanovskii V. N., Zykov M. P., Kodina G. E., Malysheva A. O., Filyanin O. A., Nepomnyashchii O. N. Extraction centrifugal generator <sup>188</sup>Re and radiopharmaceuticals based on it for radionuclide therapy. Radiokhimiya. 2016;58(5):513–520. (In Russ.)
12. Lunev A., Klement’eva O., Zverev A. Studying of radiation safety of <sup>188</sup>Re-labeled MAA preparation for treatment of resistant synovitis. Мedical Radiology and Radiation Safety. 2020;65(6):38–46. DOI: 10.12737/1024-6177-2020-65-6-38-46.
13. Kodina G. E. Radiopharmaceutical composition for radiosynovectomy and the method for its production. Patent RUS № RU 2624237. 03.07.2017. Byul. № 19. Available at: https://yandex.ru/patents/doc/RU2624237C1_20170703. Accessed: 07.11.2024. (In Russ.)
14. Zverev A. V., Dorvatovsky S. A., Petriev V. M., Skvortsov V. G., Kaprin A. D., Antonyuk A. V., Laskovets E. Yu. Radiopharmaceutical composition for the treatment of inflammatory joint diseases based on the radionuclide <sup>188</sup>Re and human blood albumin microspheres, as well as the composition and method for its production. Patent RUS № RU 2698101. 08.22.2019. Byul. № 24. (In Russ.)
15. Stepchenkova E. D., Tishchenko V. K., Vlasova O. P., Petriev V. M., Legkodimova N. S., Krylov V. V., Fedorova A. V., Kuzenkova E. A., Ostroukhoff A. A., Shegai P. V. Radioactivity distribution in the blood and urine of patients receiving systemic therapy with a <sup>177</sup>Lu radiopharmaceutical and local (intra-articular) therapy with a <sup>188</sup>Re radiopharmaceutical. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation. 2022;12(4):404–414. (In Russ.) DOI: 10.30895/1991-2919-2022-12-4-404-414.
16. Filatova Yu. S., Gawert V. R. Intra-articular hyaluronic acid: dependence of the effect on molecular weight. Russian Medical Inquiry. 2021;5(3):156–161. (In Russ.) DOI: 10.32364/2587-6821-2021-5-3-156-161.
17. Gonzales G. R., Stevenson N. R. Hyaluronan sn-117m colloid for radiosynoviorthersis and symptomatic therapy related applications. United States patent US WO 2017/062420 A1. 13.04.2017. Available at: https://patents.google.com/patent/WO2017062420A1/en. Accessed: 07.11.2024.
18. Skuridin V. S. Pharmaceutical technology. Methods and technologies for obtaining radiopharmaceuticals. Moscow: Yurait; 2024. 139 p. (In Russ.)
19. Belozertseva I. V., Blinov D. V., Krasilshchikova M. S., editors. Guide to the Care and Use of Laboratory Animals. Moscow: IRBIS; 2017. 336 р. (In Russ.)
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For citations:
Mayorov K.V., Beloglazova N.D., Sashova N.G., Kodina G.E., Malysheva A.O., Klementyeva O.E. On the possibility of using hyaluronic acid in a composition with rhenium-188 for radiosynoviorthesis. Drug development & registration. 2025;14(2):28-36. (In Russ.) https://doi.org/10.33380/2305-2066-2025-14-2-1966