Calculation of doses to the public in contact with patients underwent radiopharmaceutical therapy with ¹⁷⁷Lu: model multi-factor study

INTRODUCTION: Associated with the development of radiopharmaceutical therapy with ¹⁷⁷Lu (¹⁷⁷Lu-DOTA-TATE, ¹⁷⁷Lu-PSMA-617), the issue of radiation protection of the public becomes important. Nowadays, national regulatory and methodological documents on radiation safety do not contain release criteria of patients after radiopharmaceutical therapy with ¹⁷⁷Lu. Existing approaches to determining the release criteria after radiopharmaceutical therapy do not consider radiation exposure from the patient during long-term contact with the patient (up to several days in a confined space) and possible of generation of biological waste containing ¹⁷⁷Lu in public transport during the first hours and days after release. In order to choose an optimal approach to determine release criteria, it is necessary to assess the radiation exposure from the patient on different categories of people from the public.

OBJECTIVE: Estimation of radiation exposure of people from public from patient after radiopharmaceutical therapy with ¹⁷⁷Lu considering the radioactive biological waste containing ¹⁷⁷Lu.

MATERIALS AND METHODS: The time of patient release from the hospital was determined upon reaching the previously proposed release criteria based on the patient dose rate. The ambient dose equivalent rate for the patient after therapy with ¹⁷⁷Lu labeled radiopharmaceuticals were determined based on the experimental data available in the literature. Various scenarios of exposure of individuals in contact with the patient after release from the hospital were developed; effective doses after contact with the patient were estimated based on the developed scenarios. The activity of ¹⁷⁷Lu generated in patient biological waste after therapy was determined as well. Based on the assessments, activity concentration of ¹⁷⁷Lu was determined in wastewater of residential sewage systems and in transport during patient traveling to the place of residence. Using specialized MCNP software, the doses of public exposure in transport from ¹⁷⁷Lu generated in wastewater in tanks of transport biotoilets were modeled and estimated.

RESULTS: Doses to some categories of people from the public after the contact with a patient released immediately after administration of a radiopharmaceutical with ¹⁷⁷Lu may exceed the dose limit of 1 mSv, but release in 4–6 hours after therapy when the release criterion is reached, established in accordance with the approach of NRB-99/2009, will not lead to dose limit exceedance. The activity concentration of ¹⁷⁷Lu, generated in transport biotoilet tanks after the patient with ¹⁷⁷Lu travelling, exceeds the limit value for classifying liquid waste as radioactive (0.025 kBq/g). Doses to passengers and crew members may be higher than 100 μSv. Doses from a patient may be higher than 1 mSv after release of patient in 4–6 hours in the case of a long-distance travel (several days on a train).

DISCUSSION: Exceeding the dose limit to the public is unacceptable and therefore the patient cannot be released immediately after ¹⁷⁷Lu administration. Due to the likelihood of exceeding passenger and crew dose limits in transport during long-distance travel of a patient with administered ¹⁷⁷Lu, it is necessary to limit the travel of patients by long-distance trains.

CONCLUSION: To ensure radiation safety of the public, the optimal approach is the previously used approach when establishing release criteria in NRB-99/2009 for other radionuclides. According to this approach, the value of the release criterion for the dose rate at 1 meter from the patient after therapy with ¹⁷⁷Lu is 29 μSv/h. The greatest questions in terms of radiation safety arise when releasing non-residence patients who will have to get to their place of residence in distant regions. Thus, it is reasonable to limit the patient traveling after radiopharmaceutical therapy with ¹⁷⁷Lu using long-distance trains (instead of it is recommended to use air transport).

1. George S.C., Samuel E.J.J. Developments in 177Lu-based radiopharmaceutical therapy and dosimetry // Front Chem. 2023. Vol. 11. Р. 1218670. doi: 10.3389/fchem.2023.1218670. Erratum in: Front Chem. 2024. Vol. 11. Р. 1410803. doi: 10.3389/fchem.2024.1410803.

2. Lu X., Lu C., Yang Y., Shi X. et. al. Current Status and Trends in Peptide Receptor Radionuclide Therapy in the Past 20 Years (2000–2019): A Bibliometric Study // Front Pharmacol. 2021. Vol. 12. Р. 624534. doi: 10.3389/fphar.2021.624534.

3. Kurth J., Krause B.J., Schwarzenböck S.M. et al. External radiation exposure, excretion, and effective half-life in 177Lu-PSMA-targeted therapies // EJNMMI Res. 2018. Vol. 8, No. 1. Р. 32. doi: 10.1186/s13550-018-0386-4.

4. Garbusov P.I., Narkevich B.Ja. Are there any Perspectives for Radioiodine Treatment in Patients with Hyperthyroidism in Russia? Clinical and experimental thyroidology, 2009, Vol. 5, No. 1, рр. 3–7 (In Russ.). doi: 10.14341/ket2009513-7.

5. Balonov M.I., Golikov V.Yu., Zvonova I.A. Radiological criteria for patient release from clinic after radionuclide therapy of brachytherapy with sealed source implantation. Radiation Hygiene, 2009, Vol. 2, No. 4, pp. 5–9 (In Russ.).

6. Zvonova I., Balonov M., Golikov V. Release criteria for patients having undergone radionuclide therapy and criteria or their crossing the state border of the Russian Federation. Radiation Protection Dosimetry, 2011, Vol. 147, No. 1–2, pp. 254–257 (In Russ.). doi: 10.1093/rpd/ncr308.

7. International Commission on Radiological Protection. Release of patients after therapy with unsealed radionuclides. ICRP Publication 94 // Annual ICRP. 2004. Vol. 34 No. 2, рр. 1–79. doi: 10.1016/j.icrp.2004.08.001.

8. Narkevich B.Ya., Lysak Yu.V. Ensuring radiation safety during outpatient use of therapeutic radiopharmaceuticals. Medical radiology and radiation safety, 2015, Vol. 60, No. 4, pp. 27–35 (In Russ.).

9. Chipiga L.A., Zvonova I.A., Vodovatov A.V. et al. Improvemet of the approach to definition of patient release criteria after radionuclide therapy. Radiation Hygiene, 2023, Vol. 16, No. 2, рр. 19–31 (In Russ.). doi: 10.21514/1998-426X-2023-16-2-19-31.

10. Calais P.J., Turner J.H. Radiation safety of outpatient 177Lu-octreotate radiopeptide therapy of neuroendocrine tumors // Ann. Nucl. Med. 2014. Vol. 28, No. 6. Р. 531–539. doi: 10.1007/s12149-014-0843-8.

11. Demir M., Abuqbeitah M., Uslu-Beşli L. et al. Evaluation of radiation safety in 177Lu-PSMA therapy and development of outpatient treatment protocol // Journal of Radiological Protection. 2016. Vol. 36, No. 2. Р. 269–278. doi: 10.1088/0952-4746/36/2/269.

12. Artemyeva N.N., Baltrukova T.B. To the question of radiation protection ensuring of passengers taken radiopharmaceuticals during transportation by railway transport. Radiation Hygiene, 2013, Vol. 6, No. 4, рр. 31–34 (In Russ.).

13. Vodovatov A.V., Chipiga L.A., Ryzhov S.A. et al. Radiation accidents in X-ray and radionuclide diagnostics and therapy: comparison of Russian and international approaches to the terminology and classification. Radiation Hygiene, 2024, Vol. 17, No. 1, рр. 97–110 (In Russ.). https://doi.org/10.21514/1998-426X-2024-17-1-97-110.

14. Vodovatov A.V., Chipiga L.A., Ryzhov S.A. et al. Analysis of the radiation accidents prevalence in nuclear medicine in the Russian Federation. Radiation Hygiene, 2024, Vol. 17, No. 3, рр. 93–102 (In Russ.). doi: 10.21514/1998-426X-2024-17-3-93-102.

15. Levart D., Kalogianni E., Corcoran B., Mulholland N., Vivian G. Radiation precautions for inpatient and outpatient 177Lu-DOTATATE peptide receptor radionuclide therapy of neuroendocrine tumours // EJNMMI Phys. 2019. Vol. 6, No. 1. Р. 7. doi: 10.1186/s40658-019-0243-1.

16. International Commission on Radiological Protection. Conversion Coefficients for Radiological Protection Quantities for External Radiation Exposures. ICRP Publication. 116 // Annual ICRP. 2010. Vol. 40, No. 2–5.

17. ICRP. Radiation Dose to Patients from Radiopharmaceuticals // ICRP Publication 53. Annals of the ICRP. 1988. Vol. 18, Nо. 1–4.

18. Schuchardt C., Zhang J., Kulkarni H.R. et al. ProstateSpecific Membrane Antigen Radioligand Therapy Using 177Lu-PSMA I&T and 177Lu-PSMA-617 in Patients with MetastaticCastration-Resistant Prostate Cancer: Comparison of Safety, Biodistribution, and Dosimetry // Journal of Nuclear Medicine. 2022. Vol. 63. Р. 1199–1207. doi: 0.2967/jnumed.121.262713.

19. Krylov V.V., Legkodimova N.S., Kochetova T.Yu. et al. Radioligand therapy with 177Lu-DOTA-PSMA in metastatic castration-resistant prostate cancer. Pharmacokinetics, safety, antitumour efficacy. Diagnostic radiology and radiotherapy, 2022, Vol. 13, No. 4, рр. 75–85 (In Russ.). doi: 10.22328/2079-5343-2022-13-4-75-85.

20. Wehrmann C., Senftleben S., Zachert C. et al. Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC // Cancer Biother Radiopharm. 2007. Vol. 22, Nо. 3. Р. 406–416.

21. Chipiga L.A., Vodovatov A.V., Petryakova A.V., Zvonova I.A., Stanzhevsky A.A., Maistrenko D.N., Vazhenina D.A., Sysoev D.S. Justification of differential approach to management of patient biological waste in nuclear medicine departments. Radiation Hygiene, 2022, Vol. 15, No. 4, рр. 34–44 (In Russ.). doi: 10.21514/1998-426X-2022-15-2-19-30.

22. Chipiga L.A., Vodovatov A.V., Petryakova A.V., Zvonova I.A., Stanzhevsky A.A., Maistrenko D.N., Vazhenina D.A., Sysoev D.S. Justification of differential approach to management of patient biological waste in nuclear medicine departments. Radiation Hygiene, 2022, Vol. 15, No. 4, рр. 34–44 (In Russ.). doi: 10.21514/1998-426X-2022-15-4-34-44.