Medical Radiology and Radiation Safety. 2025. Vol. 70. № 1
DOI:10.33266/1024-6177-2025-70-1-102-108
A.V. Ozerskaya1, 2, O.N. Badmaev1, N.V. Shepelevich1, N.A. Tokarev1,
S.Y. Lipaikin1, N.G. Chanchikova1, N.A. Luzan2, А.А. Koshmanova2,
T.N. Zamay2, 3, I.I. Voronkovskii2, A.S. Lunev4, A.S. Kichkailo2, 3
Assessment of Radiation Burden on Organs and Tissues from the Aptamer-Based Radiopharmaceutical for PET/CT Imaging of Lung Cancer
1 Federal Siberian Research Clinical Center, Krasnoyarsk, Russia
2 Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia
3 Krasnoyarsk Science Center, Krasnoyarsk, Russia
4 A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia
Contact person: A.V. Ozerskaya, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Aptamers acting as the basis for radiopharmaceutical drugs based on carbon-11 have proven themselves to be highly sensitive and specific agents for imaging tumors and metastases. However, the lack of knowledge about the patterns of their metabolism in the body and the radiation exposure on organs significantly hinders their clinical use. To fill this gap, a study of the biodistribution of a radiopharmaceutical based on the carbon-11 radiolabeled aptamer LC-18, as well as an assessment of the radiation exposure on organs and tissues in vivo were carried out.
Purpose: To evaluate the doses of radiation to organs, tissues and the whole body during intravenous administration of a radiopharmaceutical based on the carbon-11 radiolabeled LC-18 aptamer to obtain information on the safety of its further application in PET/CT diagnostics
Material and methods: 11CH3-LC-18 complex was obtained in the laboratory of the Center for Nuclear Medicine of the FSRCC FMBA of Russia. Absorbed and effective doses of the drug accumulated in organs and tissues of mice were determined radiometrically. To calculate absorbed doses in organs and tissues data on the biodistribution of the 11CH3-LC-18 complex in mice were extrapolated to a model of the human body.
Results: According to the calculations it was found that the highest absorbed doses after administration of 200 MBq of a radiopharmaceutical were noted in the small intestine (3.67 ± 0.40 mGy), kidneys (2.68 ± 0.32 mGy), liver (2.00 ± 0.16 mGy), spleen (1.42 ± 0.17 mGy) and on the walls of the stomach (1.35 ± 0.14 mGy). The lowest accumulation was observed in the skin (0.48 ± 0.05 mGy), brain (0.51 ± 0.06 mGy) and thyroid gland (0.58 ± 0.06 mGy). The extrapolated absorbed doses do not exceed the thresholds noted by the UNSCEAR and ICRP.
Conclusion: The calculated predictive values of the absorbed doses in organs and tissues allow us to draw a conclusion about the safety of the studied radiopharmaceutical based on the carbon-11 labeled aptamer LC-18.
Keywords: PET, Radiopharmaceuticals, aptamers, carbon-11, absorbed doses, mice
For citation: Ozerskaya AV, Badmaev ON, Shepelevich NV, Tokarev NA, Lipaikin SY, Chanchikova NG, Luzan NA, Koshmanova АА, Zamay TN, Voronkovskii II, Lunev AS, Kichkailo AS. Assessment of Radiation Burden on Organs and Tissues from the Aptamer-Based Radiopharmaceutical for PET/CT Imaging of Lung Cancer. Medical Radiology and Radiation Safety. 2025;70(1):102–108.
(In Russian). DOI:10.33266/1024-6177-2025-70-1-102-108
References
1. Li L., Xu S., Yan H., et al. Nucleic Acid Aptamers for Molecular Diagnostics and Therapeutics: Advances and Perspectives. Angewandte Chemie. 2020;60;5:2221-2231. doi: 10.1002/anie.202003563.
2. Wang T., Chen C., Larcher L.M., Barrero R.A., Veedu R.N. Three Decades of Nucleic Acid Aptamer Technologies: Lessons Learned, Progress and Opportunities on Aptamer Development. Biotechnology Advances. 2019;37;1:28-50. doi: 10.1016/j.biotechadv.2018.11.001.
3. Zhou J., Rossi J. Aptamers as Targeted Therapeutics: Current Potential and Challenges. Rev Drug Discov. 2017;16:181-202. doi: 10.1038/nrd.2016.199.
4. Tan W., Donovan M.J., Jiang J. Aptamers from Cell-Based Selection for Bioanalytical Applications. Rev Drug Discov. 2013;113;4:2842-2862. doi: 10.1021/cr300468w.
5. Kichkailo A.S., Narodov A.A., Komarova M.A., et al. Development of DNA Aptamers for Visualization of Glial Brain Tumors and Detection of Circulating Tumor Cells. Molecular Therapy: Nucleic Acids. 2023;32:267-288. doi: 10.1016/j.omtn.2023.03.015.
6. Ozerskaya A.V., Belugin K.V., Belkin S.A., Chanchikova N.G., Tokarev N.A., Kichkaylo A.S., Zamay T.N., Barankin B.V. Sposob Polucheniya Aktivnoy Farmatsevticheskoy Substantsii dlya Sinteza Radiofarmpreparata, Tropnogo k Kletkam Kartsinomy Erlikha = Method for Obtaining an Active Pharmaceutical Substance for the Synthesis of a Radiopharmaceutical Tropic to Ehrlich Carcinoma Cells. Russian Federation Patent 2711645. Claimed 06.26.2019. Published 01.17.2020 (In Russ.).
7. Ding D., Zhao H., Wei D., Yang Q., et al. The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer. Research. 2023;6:1-12. doi: 10.34133/research.0126.
8. Granov A.M., Tyutin L.A., Kostenikov N.A., Shtukovskiy O.A., et al. Seventeen-Year Experience of Using Positron Emission Tomography in Clinical Practice (Achievements and Development Prospects). Meditsinskaya Vizualizatsiya = Medical Vizualization. 2013;2:41-52 (In Russ.).
9. Farzin L., Shamsipur M., Moassesi M.E., Sheibani S. Clinical Aspects of Radiolabeled Aptamers in Diagnostic Nuclear Medicine: A new Class of Targeted Radiopharmaceuticals. Bioorganic and Medicinal Chemistry. 2019;27;12:2282-2291. doi: 10.1016/j.bmc.2018.11.031.
10. Ivanov I.V., Ushakov I.B. Basic Approaches to the Extrapolation of Data of Animals to Human In Radiobiological Experiment. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost’ = Medical Radiology and Radiation Safety. 2020;65;3:5-12. doi: 10.12737/1024-6177-2020-65-3-5-12.
11. Estrada S., Elgland M., Selvaraju R.M., Mani K., Tegler G., et al. Preclinical Evaluation of [11C]GW457427 as a Tracer for Neutrophil Elastase. Nuclear Medicine and Biology. 2022;106:62-71. doi: 10.1016/j.nucmedbio.2022.01.001.
12. Blau M. Radiation Dosimetry of 131-I-19-Iodocholesterol: The Pitfalls of Using Tissue Concentration Data. J Nucl Med. 1975;16;3:247-9. PMID: 1113178.
13. Tolvanen T., Yli-Kerttula T., Ujula T., Autio A., Lehikoinen P., et al. Biodistribution and Radiation Dosimetry of [11C]Choline: a Comparison Between Rat and Human Data. Eur J Nucl Med Mol Imaging. 2010;37:874-883. doi: 10.1007/s00259-009-1346-z.
14. Lunev A.S., Klement’yeva O.Ye., Kodina G.V. Computational Research of Prognosis Values of Absorbed Doses for Pre-Clinical Safety Evaluation of Radiopharmaceutical 68Ga-Citrate. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost’ = Medical Radiology and Radiation Safety. 2015;60(4):19-26
(In Russ.).
15. Malakhovskiy V.N., Trufanov G.Ye., Ryazanov V.V. Radiatsionnaya Bezopasnost’ pri Radionuklidnykh Issledovaniyakh = Radiation Safety in Radionuclide Research. St. Petersburg., Meditsina Publ., 2008. 136 p. (In Russ.).
16. Cherry S.R., Dahlbom M. PET: Physics, Instrumentation, and Scanners. NY, Springer, 2006. P. 1-117. doi: 10.1007/0-387-34946-4_1.
17. Charles M. UNSCEAR Report 2000: Sources and Effects of Ionizing Radiation. United Nations Scientific Comittee on the Effects of Atomic Radiation. J Radiol Prot. 2001;21;1:83-6. doi: 10.1088/0952-4746/21/1/609.
18. International Commission on Radiation Protection (ICRP) 103 Publication. Ed. M.F.Kiselev, N.K.Shandala. Moscow, Alana Publ., 2009. 344 p. (In Russ.).
19. Xie T., Zaidi H.. Evaluation of Radiation Dose to Anthropomorphic Paediatric Models from Positron-Emitting Labelled Tracers. Phys. Med. Biol. 2014;59;5:1165-1187. doi: 10.1088/0031-9155/59/5/1165.
20. Seltzer M.A., Jahan S.A., Sparks R., Stout D.B., et al. Radiation Dose Estimates in Humans for (11)C-Acetate Whole-Body Pet. J Nucl Med. 2004;45;7:1233-6. PMID: 15235071.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The research was carried out within the state assignment of FSRCC FMBA of Russia 2022-2024 (“Synthesis, study of the specific action and safety of a new experimental drug based on a carbon-11 aptamer intended for the diagnosis of lung cancer by PET/CT”). The development of the method for synthesizing oligonucleotide and determining its structure was carried out at the expense of the Ministry of Education and Science of the Russian Federation FWES-2022-0005.
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.10.2024. Accepted for publication: 25.11.2024.