Dosimetric support for clinical trials of the alpha-emitting radiopharmaceutical Ac-225-PSMA-617 at radionuclide therapy of metastatic castration-resistant prostate cancer

«Radiation and Risk», 2025, vol. 34, No. 3, pp.30-42

DOI: 10.21870/0131-3878-2025-34-3-30-42

Authors

Stepanenko V.F. – Head of Lab., D. Sc., Biol., Prof. Contacts: 4 Korolev str., Obninsk, Kaluga region, Russia, 249035. Tel.: +7 (484) 399-70-02; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Bogacheva V.V. – Lead. Res., C. Sc., Biol.
Petukhov A.D. – Sen. Res., C. Sc., Biol
Dorokhov A.V. – Engineer-Res.
Kochetova T.Yu. – Radiologist
Sigov M.A. – Head of Dep.
Spichenkova O.N. – Lead. Engineer
Vlasova O.P. – Lead. Res., C. Sc., Biol.
Krylov V.V. – Head of Dep., MD
Smolyarchuk M.Ya. – Radiologist
Shurinov A.Yu. – Sen. Res., C. Sc., Med.
Minaeva N.G. – Scien. Secretary, C. Sc., Biol.
Ivanov S.A. – Director, Corr. Member of RAS, MD, Prof. of RUDN University Dep. A. Tsyb MRRC.
Shegay P.V. – Deputy General Director, C. Sc., Med.
Kaprin A.D. – General Director, Director of P. Hertsen MORI, Head of RUDN University Dep., Academician of RAS, MD, Prof. NMRRC.
¹ A. Tsyb MRRC, Obninsk
² NMRRC, Obninsk
³ Peoples' Friendship University of Russia named after Patrice Lumumba, Moscow
⁴ P. Hertsen MORI, Moscow

Abstract

To calculate internal radiation doses to tumors and organs at risk of patients included to clinical trials of ²²⁵Ac-PSMA-617 radiopharmaceutical, a specialized software and database package, developed at the National Medical Research Radiological Center, was used. The calculations were based on the general methodology of Medical Internal Radiation Dose (MIRD) Committee. Visualization of foci and organs at risk of patients was performed using the SPECT/CT method (Discovery NM/CT 670 system) with a high-energy collimator and recording photopeaks of gamma radiation of ²²¹Fr (218 keV) and ²¹³Bi (444 keV) at discrete points in time after the administration of the radiopharma-ceutical (1-72 hours). The values of internal equivalent doses were determined for all visualized foci and organs at risk (parotid and submandibular salivary glands, kidneys, spleen, liver). The relative biological efficiency for alpha particles was accepted to be 5. A large variability of individual radiation doses in foci was found at the same administered radiopharmaceutical’s activity: dose values differ by 7-9 times depending on individual foci volumes and individual patients’ pharmacokinetic parameters. At the same time, equivalent doses in foci tend to increase with increasing of administered radiopharmaceutical activity, and are within the following limits: 7-33 Sv (planned activity for admin-istration – 6 MBq) and 6.4-55 Sv (planned activity for administration – 9 MBq). Individual equivalent doses to organs at risk also vary significantly and are within the following limits: 0.1-1.5 Sv (salivary glands) and 0.68-8.8 Sv (kidneys, spleen, liver), which is less than the “commonly applied dose con-straints” in radiotherapy. The data obtained are necessary for the analysis of the effectiveness and safety of the ²²⁵Ac-PSMA-617 radiopharmaceutical and allow optimizing the choice of radiopharma-ceutical’s activity individually for each patient.

Key words
internal dosimetry, individual radiation doses, radiopharmaceuticals, alpha emitters, Ac-225, radiation therapy, clinical trials, nuclear medicine.

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