Issues
Computational and experimental evaluation of absorbed doses in gold nanoparticles mediated contrast enhanced radiotherapy for tumor-bearing laboratory animals
«Radiation and Risk», 2025, vol. 34, No. 1, pp.115-127
DOI: 10.21870/0131-3878-2025-34-1-115-127
Authors
Finogenova Yu.A. – Researcher. Contacts: 24, Kashirskoe sh., Moscow, Russia, 115478. Tel.: +7(915)418-99-23; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .Skribitsky V.A. – Jun. Researcher
Lipengolts A.A. – Lead. Researcher, C. Sc., Phys.-Math.
Shpakova K.E. – Lab. Assistant
Smirnova A.V. – Sen. Researcher, C. Sc., Biol.
Grigorieva E.Yu. – Head of Lab., D. Sc., Biol. N.N. Blokhin NMRCO.
Kasianov A.A. – Post. Student
Sozaev I.V. – Engineer
Klimentov S.M. – Deputy Director, C. Sc., Phys.-Math. MEPhI.
1 Blokhin National Medical Research Center of Oncology of the Ministry of Health of the RF, Moscow
2 National Research Nuclear University MEPhI, Moscow
3 Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Moscow
4 The Loginov Moscow Clinical Scientific Center of Moscow Health Department, Moscow
5 Vladimir State University named after Alexander and Nikolay Stoletovs, Vladimir
Abstract
Contrast-enhanced radiotherapy (CERT) is a method of radiation therapy based on the interaction of a dose-enhancing agent with external X-ray radiation. Gold nanoparticles are a promising dose-enhancing agent. The aim of the work is to determine the maximum concentration of gold and corresponding dose enhancement factor (DEF) in healthy organs and tumor node after intravenous injec-tion of nanoparticles to tumor-bearing mice, according to computed tomography data. Mice with subcutaneous syngeneic tumors were used for the study: melanoma B16F10 (n=5); adenocarcinoma Ca755 (n=5); EMT6 (n=5); 4T1 (n=5). Laser-ablated gold nanoparticles with a diameter of 8.3 nm were injected intravenously to mice at a dosage of 1000 mg Au/kg body weight. computed tomography scans were acquired before nanoparticle injection, then immediately after injection and after 1, 4, 24, 48 h and 5 days. Using a linear calibration relationship, the increase in tissue radiodensity was recalculated into the concentration of gold. The local increase in the absorbed dose was estimated using the analytical dependence of DEF on the concentration of gold nanoparticles for X-rays with a maximum energy of 140 kV. The maximum concentration of gold in the tumor was determined for 4 tumor models. The calculated DEF ranged from 1.3+-0.2 for B16F10 melanoma to 1.6+-0.2 for 4T1 adenocarcinoma. At 48 h after injection, there were also high concentrations of gold in blood (DEF for heart wall from 1.5+-0.2) and in liver tissue (DEF from 1.4+-0.1). 4T1 adenocarcinoma is an optimal tumor model for further in vivo studies of CERT. High concentration of gold in heart chambers and in liver tissue limits the application of CERT for lung, mediastinal and abdominal tumors. CERT is most applicable for tumors of brain and extremities.
Key words
gold nanoparticles, laser-ablated nanoparticles, dose enhancement factor, radiotherapy, computed tomography, tumor models, subcutaneous tumors, syngeneic tumors, melanoma, adeno-carcinoma, mice, radiobiology.
References
1. Sheino I.N., Izhevskij P.V., Lipengolts A.A., Kulakov V.N., Wagner A.A., Sukhikh E.S., Varlachev V.A. Development of binary technologies of radiotherapy of malignant neoplasms: condition and problems. Byulleten’ sibirskoi meditsiny – Bulletin of Siberian Medicine, 2017, vol. 16, no. 3, pp. 192-209. (In Russian).
2. Lipengolts A.A., Skribitsky V.A., Finogenova Y.A., Shulyak A.T., Abakumov M.A., Bykov A.Y., Grigorieva E.Y., Smirnova A.V., Shpakova K.E., Zhizhin K.Y. Hafnium complexes as contrast media and dose enhancing agents for radiology and contrast-enhanced radiotherapy. Biophysics, 2024, vol. 69, no. 1, pp. 148-155.
3. Rose J.H., Norman A., Ingram M., Aoki C., Solberg T., Mesa A. First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx). Int. J. Radiat. Oncol. Biol. Phys., 1999, vol. 45, no. 5, pp. 1127-1132.
4. Finogenova Y.A., Lipengolts A.A., Skribitsky V.A., Shpakova K.E., Smirnova A.V., Skribitskaya A.V., Sycheva N.N., Grigorieva E.Y. Metal nanoparticles as radiosensitizers for cancer radiotherapy in vivo. Meditsinskaya fizika – Medical Physics, 2023, no. 3, pp. 70-86. (In Russian).
5. Skrodzki D., Molinaro M., Brown R., Moitra P., Pan D. Synthesis and bioapplication of emerging nano-materials of hafnium. ACS Nano, 2024, vol. 18, no. 2, pp. 1289-1324.
6. Thivat E., Casile M., Moreau J., Molnar I., Dufort S., Seddik K., Le Duc G., De Beaumont O., Loeffler M., Durando X., Biau J. Phase I/II study testing the combination of AGuIX nanoparticles with radiochemotherapy and concomitant temozolomide in patients with newly diagnosed glioblastoma (NANO-GBM trial protocol). BMC Cancer, 2023, vol. 23, no. 1, pp. 344. DOI: 10.1186/s12885-023-10829-y.
7. Gerken L.R., Gerdes M.E., Pruschy M., Herrmann I.K. Prospects of nanoparticle-based radioenhancement for radiotherapy. Mater. Horiz., 2023, vol. 10, pp. 4059-4082.
8. Hainfeld J.F., O’Connor M.J., Dilmanian F.A., Slatkin D.N., Adams D.J., Smilowitz H.M. Micro-CT enables microlocalisation and quantification of Her2-targeted gold nanoparticles within tumour regions. Br. J. Radiol., 2011, vol. 84, no. 1002, pp. 526-533.
9. Skribitsky V.A., Pozdniakova N.V., Lipengolts A.A., Popov A.A., Tikhonowski G.V., Finogenova Y.A., Smirnova A.V., Grigorieva E.Y. A spectrophotometric method for estimation of the size and concentration of laser ablated gold nanoparticles. Biophysics, 2022, vol. 67, no. 1, pp. 22-26.
10. Roeske J.C., Nunez L., Hoggarth M., Labay E., Weichselbaum R.R. Characterization of the theorectical radi-ation dose enhancement from nanoparticles. Technol. Cancer Res. Treat., 2007, vol. 6, no. 5, pp. 395-401.
11. Duval K.E.A., Aulwes E., Zhang R., Rahman M., Ashraf M.R., Sloop A., Sunnerberg J., Williams B.B., Cao X., Bruza P., Kheirollah A., Tavakkoli A., Jarvis L.A., Schaner P.E., Swartz H.M., Gladstone D.J., Pogue B.W., Hoopes P.J. Comparison of tumor control and skin damage in a mouse model after ultra-high dose rate irradiation and conventional irradiation. Radiat. Res., 2023, vol. 200, no. 3, pp. 223-231.
12. Lipengolts A.A., Cherepanov A.A., Pervova V.V., Kulakov V.N., Grigorieva E.Y., Sheino I.N. Mammary adenocarcinoma Ca755 as a tumor model for experimental radiotherapy. Meditsinskaya fizika – Medical Physics, 2016, no. 4, pp. 80-83. (In Russian).
13. Elnikova A.A. Tumor microenvironment – a dark horse in anticancer chemotherapy. Zdorovye i obrazovanie v XXI veke – Health and Education at XXI century, 2015, vol. 17, no. 1, pp. 84-86. (In Russian).
14. Bogdanova I.M., Boltovskaya M.N., Rakhmilevich A.L., Artemyeva K.А. Key role of tumor-associated macrophages in the progressing and metastasis of tumors. Immunologiya – Immunology, 2019, vol. 40, no. 4, pp. 41-47. (In Russian).
15. Lipengolts A.A., Vorobyeva E.S., Cherepanov A.A., Abakumov M.A., Abakumova T.O., Smirnova A.V., Finogenova Y.A., Grigorieva E.Y., Sheino I.N., Kulakov V.N. Evaluation of absorbed dose distribution in melanoma B16B10 during contrast enhanced radiotherapy with intratumoral administration of dose-enhancing agent. Vestnik Rossiyskogo godudarstvennogo meditsinskogo universiteta – Bulletin of RSMU, 2018, no. 5, pp. 70-75. (In Russian).
16. Hainfeld J.F., Slatkin D.N., Smilowitz H.M. The use of gold nanoparticles to enhance radiotherapy in mice. Phys. Med. Biol., 2004, vol. 49, no. 18, pp. N309-N315.
17. Skribitsky V.A., Finogenova Y.A., Lipengolts A.A., Pozdniakova N.V., Smirnova A.V., Shpakova K.E., Grigorieva E.Y. In vivo studies of laser-ablated gold nanoparticles as dose enhancers for binary radiotherapy of cancer. Phys. At. Nuclei, 2022, vol. 85, no. 9, pp. 1598-1602.
18. Nosrati H., Seidi F., Hosseinmirzaei A., Mousazadeh N., Mohammadi A., Ghaffarlou M., Danafar H., Conde J., Sharafi A. Prodrug polymeric nanoconjugates encapsulating gold nanoparticles for enhanced X-ray radiation therapy in breast cancer. Adv. Healthc. Mater., 2022, vol. 11, no 3, pp. e2102321. DOI: 10.1002/adhm.202102321.
19. Yang C., Gao Y., Fan Y., Cao L., Li J., Ge Y., Tu W., Liu Y., Cao X., Shi X. Dual-mode endogenous and exogenous sensitization of tumor radiotherapy through antifouling dendrimer-entrapped gold nanoparticles. Theranostics, 2021, vol. 11, no 4, pp. 1721-1731.
20. Dou Y., Guo Y., Li X., Li X., Wang S., Wang L., Lv G., Zhang X., Wang H., Gong X., Chang J. Size-tuning ionization to optimize gold nanoparticles for simultaneous enhanced CT imaging and radiotherapy. ACS Nano, 2016, vol. 10, no. 2, pp. 2536-2548.
Full-text article (in Russian)