Radioligand therapy with 177Lu-DOTA-PSMA in metastatic castration-resistant prostate cancer. Pharmacokinetics, safety, antitumour efficacy
V. V. Krylov,
N. S. Legkodimova,
T. Yu. Kochetova,
V. M. Petriev,
M. A. Sigov,
V. K. Tishchenko,
A. I. Pronin,
A. Yu. Shurinov,
K. M. Petrosyan,
O. N. Spichenkova,
O. B. Karyakin,
V. A. Biryukov,
V. F. Stepanenko,
O. P. Vlasova,
P. V. Shegaj,
S. A. Ivanov,
A. D. Kaprin https://doi.org/10.22328/2079-5343-2022-13-4-75-85
Abstract
INTRODUCTION: The results of studies of clinical potential of a new domestic radiopharmaceutical 177Lu-DOTA-PSMA in patients with metastatic castration-resistant prostate cancer are presented in this article.
OBJECTIVE: The pharmacokinetics, safety and tolerability of radiopharmaceutical were studied. Tolerability of increasing activities — 5.0, 7.5 and 10.0 GBq was investigated.
MATERIALS AND METHODS: The study included 12 patients with metastatic castration-resistant prostate cancer, who progressed after previous treatment. The first 4 patients was treated by 5 GBq of 177Lu DOTA-PSMA, the next 4 patients of the second group was treated by 7.5 GBq, and the 4 patients of the third group was treated by 10 GBq. Radiopharmacokinetics was studied by whole-body scintigraphy, SPECT/CT, blood and urine radiometry. The radiation-absorbed dose (RAD) of metastases and organs at risk was studied by clinical dosimetry. Safety assessment also was studied by hematological status. All patients was taken a complete blood count, a biochemical blood test before course of therapy treatable and during the case study.
RESULTS: Study data showed high accumulation of 177Lu-DOTA-PSMA the in pathological focus, the distribution in the body conformed to the previous data of PET/CT study. Blood radiometry showed that 177Lu-DOTA-PSMA rapidly excreted from the bloodstream (during the first hours after injection). Urine radiometry showed that, more than half of the injected dose was excreted during 2 days (from 34.4% to 88.8%).
DISCUSSION: During the study was solicited increasing of pain syndrome, dry mouth. Most patients had moderate myelosuppression. Changes in hematological parameters had a transistor character, the adverse event resolved without consequences in 5 week. 4th grade of NCI CTCAE hematological toxicity criteria wasn’t identified. Serious adverse events weren’t identified too.
CONCLUSIONS: Radiopharmaceutical demonstrated high affinity for tumor tissue and safety in the clinical use. Data, which demonstrating a high potential anti-tumor efficacy of radiopharmaceutical, were obtained. Dosimetric studies showed radiation safety of work with radiopharmaceutical for the personnel.
Keywords
metastatic castration-resistant prostate cancer,
radionuclide therapy,
radioligand therapy,
radiopharmaceutical,
177Lu-DOTA-PSMA
Supporting agencies: The study was financially supported by the Ministry of Health of the Russian Federation as part of the state assignment (in 2021–2023) «Clinical trials of radiopharmaceutica based on prostate-specific ligand and lutetium-177 (177Lu) for radioligand therapy of metastatic castration-resistant prostate cancer».
About the Authors
V. V. Krylov
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC; Obninsk Institute for Nuclear Power Engineering
Russian Federation
Russian Federation
Valeriy V. Krylov — Dr. of Sci. (Med.), head of the department of radiosurgical treatment with open radionuclides
10 Zhukov str., Obninsk, Kaluga region, 249031
N. S. Legkodimova
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC; Frumkin Institute of Physical Chemistry and Electrochemistry
Russian Federation
Russian Federation
Nadezhda S. Legkodimova — medical resident of the department of radiosurgical treatment with open radionuclides
10 Zhukov str., Obninsk, Kaluga region, 249031
T. Yu. Kochetova
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Tatiana Yu. Kochetova — researcher of the department of radiosurgical treatment with open radionuclides
10 Zhukov str., Obninsk, Kaluga region, 249031
V. M. Petriev
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC; Moscow Engineering Physics Institute
Russian Federation
Russian Federation
Vasiliy M. Petriev — Dr. of Sci. (Biol.), head of the laboratory of experimental nuclear medicine; professor of National Research Nuclear University MEPhI
10 Zhukov str., Obninsk, Kaluga region, 249031;
31 Kashirskoe av., Moscow, 115409
M. A. Sigov
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Michail A. Sigov — head of the radionuclide diagnostic department
10 Zhukov str., Obninsk, Kaluga region, 249031
V. K. Tishchenko
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Viktoria K. Tishchenko — Dr. of Sci. (Biol.), leading researcher of the laboratory of experimental nuclear medicine
10 Zhukov str., Obninsk, Kaluga region, 249031
A. I. Pronin
N.N.Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Artem I. Pronin — Cand. of Sci. (Med.), head of department of radioisotope diagnostics and therapy, head of the positron emission tomography department
23 Kashirskoe av., Moscow, 115478
A. Yu. Shurinov
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Andrey Yu. Shurinov — researcher of the department of radiosurgical treatment with open radionuclides
10 Zhukov str., Obninsk, Kaluga region, 249031
K. M. Petrosyan
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Karina M. Petrosyan — senior researcher of the department of radiosurgical treatment with open radionuclides
10 Zhukov str., Obninsk, Kaluga region, 249031
O. N. Spichenkova
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Olga N. Spichenkova — leading engineer of the radionuclide diagnostic department
10 Zhukov str., Obninsk, Kaluga region, 249031
O. B. Karyakin
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
V. A. Biryukov
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
V. F. Stepanenko
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Valeriy F. Stepanenko — Dr. of Sci. (Biol.), head of the laboratory of medical and environmental dosimetry and radiation safety
10 Zhukov str., Obninsk, Kaluga region, 249031
O. P. Vlasova
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC; National Medical Research Radiological Centre
Russian Federation
Russian Federation
Oksana P. Vlasova — Cand. of Sci. (Biol.), head of grants and external contracts department of the centre of innovative radiological and regenerative technologies
4 Korolyova str., Obninsk, Kaluga region, 249036
P. V. Shegaj
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Petr V. Shegaj — Cand. of Sci. (Med.), head of the centre of innovative radiological and regenerative technologies
4 Korolyova str., Obninsk, Kaluga region, 249036
S. A. Ivanov
A.F.Tsyb Medical Radiological Research Centre — FSBI NMRRC
Russian Federation
Russian Federation
Sergey A. Ivanov — Dr. of Sci. (Med.), professor, corresponding member of the Russian Academy of Sciences, director
10 Zhukov str., Obninsk, Kaluga region, 249031
A. D. Kaprin
National Medical Research Radiological Centre; Рeoples Friendship University of Russia
Russian Federation
Russian Federation
Andrey D. Kaprin — Dr. of Sci. (Med.), professor, Academician of the Russian Academy of Sciences, general director; head of the department of urology and operative nephrology with a course of oncourology of Medical Institute of RUDN University
4 Korolyova str., Obninsk, Kaluga region, 249036;
6 Miklukho-Maklaya str., Moscow, 117198
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Review
For citations:
Krylov V.V., Legkodimova N.S., Kochetova T.Yu., Petriev V.M., Sigov M.A., Tishchenko V.K., Pronin A.I., Shurinov A.Yu., Petrosyan K.M., Spichenkova O.N., Karyakin O.B., Biryukov V.A., Stepanenko V.F., Vlasova O.P., Shegaj P.V., Ivanov S.A., Kaprin A.D. Radioligand therapy with 177Lu-DOTA-PSMA in metastatic castration-resistant prostate cancer. Pharmacokinetics, safety, antitumour efficacy. Diagnostic radiology and radiotherapy. 2022;13(4):75-85. (In Russ.) https://doi.org/10.22328/2079-5343-2022-13-4-75-85
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