Pharmacokinetic modeling and dosimetric planning of radionuclide therapy of bone metastases

«Radiation and Risk», 2022, vol. 31, No. 1, pp.49-63

DOI: 10.21870/0131-3878-2022-31-1-49-63

Authors

Matveev A.V. – Associate Prof., C. Sc., Phys.-Math. Dostoevsky OmSU. Contacts: 55A Mira av., Omsk, Russia, 644077. Tel.: +79043251774; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Dostoevsky Omsk State University, Omsk

Abstract

This paper discusses the features of modeling and calculating the pharmacokinetic and dosimetric characteristics of osteotropic radiopharmaceuticals based on a compartment model of their transport in the human body with bone metastases. A software package for pharmacokinetic modeling and dosimetric planning of palliative radionuclide therapy of bone metastases using clinical radiometric data has been developed and tested. Within the framework of the four-compartment model, a method for determining absorbed doses in critical organs and tissues through their masses and through S-factors is proposed. Three approaches to the appointment of the activity of a radiopharmaceutical and the features of individual dosimetric planning of radionuclide therapy of bone metastases are considered and analyzed. For 10 patients with bone metastases, individual kinetic parameters of transport (transport constants of the model) of the radiopharmaceutical "¹⁵³Sm-oxabifor" were identified during its intravenous intake into the body and calculations of absorbed doses in bone tissues and metastases, the circulatory system, kidneys and bladder were performed, taking into account its periodic emptying. It is shown that when the standard and specific activities of ¹⁵³Sm-oxabifor are introduced into the patient's body (the first and second approaches), the absorbed doses in 10 patients differ by 5-6 times, while cases of under- or over-irradiation of bone tissues with metastases are detected, which can significantly reduce the effectiveness of radionuclide therapy or adversely affect the patient's condition later. The individual injectable activity of 153Sm-oxabifor calculated within the framework of the third approach for 10 patients varies widely from 19 to 165 mCi, while there are no cases of under- or over-irradiation of bone tissues. The dose loads on the circulatory system, kidneys and bladder for all patients are tolerant and do not exceed the maximum permissible values.

Key words
modeling, pharmacokinetics, dosimetric planning, radiopharmaceutical, nuclear medi-cine, radionuclide therapy, bone metastases, samarium-153, absorbed doses, S-values.

References

1. Murray I., Du Y. Systemic radiotherapy of bone metastases with radionuclides. Clin. Oncol., 2021, vol. 33, no. 2, pp. 98-105.

2. Handkiewicz-Junak D., Poeppel T.D., Bodei L., Aktolun C., Ezziddin S., Giammarile F., Delgado-Bolton R.C., Gabriel M. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides. Eur. J. Nucl. Med. Mol. Imaging, 2018, vol. 45, no. 5, pp. 846-859.

3. Krylov V.V., Drozdovsky B.Ya., Tsyb A.F. Radionuclide therapy in palliative treatment of patients with bone metastases. Palliativnaya medicina i reabilitaciya – Palliative Medicine and Rehabilitation, 2005, no. 3, pp. 45-53. (In Russian).

4. Juzha D.A., Sagan D.L. Palliative radionuclide therapy of bone metastases. Promeneva dіagnostika, promeneva terapіya – Radiation Diagnostics, Radiation Therapy, 2010, no. 1, pp. 65-69. (In Russian).

5. Klimanov V.A. Radiobiological and dosimetric planning of radiation and radionuclide therapy. Part 2. Moscow, MEPhI, 2011. 604 p. (In Russian).

6. Zyryanov S.K., Zatolochina K.E. Prospects for the use of radionuclide drugs in the treatment of malignant neoplasms in the Russian Federation. Kachestvennaya klinicheskaya praktika – Qualitative Clinical Practice, 2018, no. 2, pp. 51-57. (In Russian).

7. Petriev V.M., Afanas’eva, E.L., Skvortsov, V.G. Osteotropic radiopharmaceuticals based on phosphonic acids for the treatment of bone metastases in humans (review). Khimiko-farmatsevticheskiy zhurnal – Pharmaceutical Chemistry Journal, 2008, vol. 42, no. 5, pp. 233-240. (In Russian).

8. Pacilio M., Ventroni G., Basile C., Ialongo P., Becci D., Mango L. Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone metastases with 153Sm-EDTMP. Eur. J. Nucl. Med. Mol. Imaging, 2014, vol. 41, no. 2, pp. 238-252.

9. Duflot V.R., Ermakov V.S., Lobanova E.I., Voroncova M.S., Venediktova J.B., Pankratov A.A., Petriev Yu.M., Tishchenko V.K. Preclinical studies of radiopharmaceutical based on thermo-sensitive copolymer and samarium-153 for local radionuclide therapy of solid tumors. Onkologicheskij zhurnal: luchevaya diagnostika, luchevaya terapiya – Journal of Oncology: Diagnostic Radiology and Radiotherapy, 2018, vol. 1, no. 4, pp. 72-81. (In Russian).

10. Tishchenko V.K., Petriev V.M., Smorizanova O.A., Mikhailovskaya A.A. Effect of chemical structure of some phosphonic acids labeled with Re-188 on their behavior in laboratory animals. Radiatsiya i risk – Radiation and Risk, 2017, vol. 26, no. 1, pp. 78-88. (In Russian).

11. Stepanenko V.F., Yaskova E.K., Belukha I.G., Petriev V.M., Skvortsov V.G., Kolyzhenkov T.V., Petukhov A.D., Dubov D.V. The calculation of internal irradiation of nano-, micro- and macro-biostructures by electrons, beta particles and quantum radiation of different energy for the development and research of new radiopharma-ceuticals in nuclear medicine. Radiatsiya i risk – Radiation and Risk, 2015, vol. 24, no. 1, pp. 35-60. (In Russian).

12. Sergienko V.I., Jelliffe R., Bondareva I.B. Applied pharmacokinetics: basic provisions and clinical applica-tion. Moscow, Publishing House of the Russian Academy of Medical Sciences, 2003. 208 p. (In Russian).

13. Kotina E.D. Software complex "Diagnostics" for processing radionuclide studies. Vestnik Sankt-Peterburg-skogo universiteta – Bulletin of the St. Petersburg University, 2010, no. 2, pp. 100-113. (In Russian).

14. Matveev A.V., Korneeva M.Yu. Model of the kinetics of an osteotropic radiopharmaceutical and determination of absorbed doses in radionuclide therapy of bone metastases. Vestnik Omskogo universiteta – Herald of the Omsk University, 2018, vol. 23, no. 1, pp. 35-42. (In Russian).

15. Dolya O.P., Matusevich E.S., Klepov A.N., Kurachenko Yu.A. Dosimetric support of radionuclide diagnos-tics and therapy of bone metastases. Al'manah klinicheskoj meditsiny – Almanac of Clinical Medicine, 2008, vol. 17, pp. 310-313. (In Russian).

16. Matveev A.V., Korneeva M.Yu. Pharmacokinetic modeling and calculation of absorbed doses in radionuclide therapy of bone metastases. Svidetel'stvo o gosudarstvennoj registracii programmy dlya EVM – Certificate of state registration of the computer program, RU 2018616431, 01.06.2018. Application No. 2018613961 dated 19.04.2018. (In Russian).

17. Dolya O.P., Klepov A.N., Krylov V.V., Drozdovsky B.Ya., Matusevich E.S. Dynamics of accumulation and excretion of 153Sm-oxabifor in patients with bone metastases during radionuclide therapy. Radiatsiya i risk – Radiation and Risk, 2007, vol. 16, no. 2-4, pp. 39-47. (In Russian).

18. Dolya O.P., Matusevich E.S., Klepov A.N. Mathematical modeling of the kinetics of transport of an osteo-tropic radiopharmaceutical in the body of patients with bone metastases. Meditsinskaya fizika – Medical Physics, 2007, no. 2, pp. 40-50. (In Russian).

19. Bouchet L.G., Bolch W.E., Howell R.W., Rao D.V. S values for radionuclides localized within the skeleton. J. Nucl. Med., 2000, vol. 41, no. 1, pp. 189-212.

20. ICRP, 1982. The limits of the receipt of radionuclides for working with ionizing radiation. Publication ICRP 30. Moscow, Energoatomizdat, 1982. (In Russian).

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