Medical Radiology and Radiation Safety. 2025. Vol. 70. № 1
DOI:10.33266/1024-6177-2025-70-1-109-114
V.I. Chernov1, 2, 3, A.N. Rybina1, R.V. Zelchan1, 2, A.A. Medvedeva1, O.D. Bragina1, 2,
N.A. Lushnikova1, E.A. Usynin1, A. Abouzayed4, S.S. Rinne4, J. Sörensen5,
V.М. Tolmachev2, 6, A.М. Orlova2, 4, 7
The Gastrin-Releasing Peptide Receptor Antagonist [99MTc]Tc-Rm26 is a Novel Radiopharmaceutical for Prostate Cancer Imaging
1 Scientific Research Institute of Oncology, Tomsk National Research Medical Center, Tomsk, Russia
2 Oncoteranostics Research Center, Scientific Research School of Chemistry and Applied Biomedical
Sciences, Polytechnic University, Tomsk, Russia
3 National Research Center ‟Kurchatov Institute”, Moscow, Russia
4 Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
5 Department of Surgical Sciences, Nuclear Medicine & PET, Uppsala University, Uppsala, Sweden
6 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
7 Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Contact person: V.I. Chernov, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Gastrin releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PC). Currently, radiopharmaceuticals (RP) for visualization of GPRP based on bombesin antagonists are developed. The aim of the present work was to conduct a phase I clinical trial of the GRPR antagonist [99mTc]Tc-RM26 and to study the possibility of its use for PC SPECT imaging. Thirteen patients diagnosed with PC were included in the study. Patients received [99mTc]Tc-RM26 intravenous bolus at a dose of 640±165 MBq (40 μg/injection). Six patients underwent whole-body planar imaging and SPECT/CT at 2, 4, 6, and 24 h after injection. Seven patients had SPECT/CT alone performed 2 h after RFP injection. The study showed that a single intravenous injection of [99mTc]Tc-RM26 is safe and well tolerated. Critical organs for RFP are the gallbladder, small intestine, upper colon and kidney. The dose burden per patient associated with the administration of [99mTc]Tc-RM26 RFP is 3–6 mSv per study. The studied RP allows to visualize primary prostate malignant tumors, as well as its metastases to lymph nodes and bones. It is reasonable to conduct further clinical studies of [99mTc]Tc-RM26 to evaluate the sensitivity and specificity of SPECT/CT with this RP for diagnostics and staging of prostate cancer.
Keywords: prostate cancer, gastrin-releasing peptide receptor antagonist, [99mTc]Tc-RM26, SPECT
For citation: Chernov VI, Rybina AN, Zelchan RV, Medvedeva AA, Bragina OD, Lushnikova NA, Usynin EA, Abouzayed A, Rinne SS, Sörensen J, Tolmachev VМ, Orlova AМ. The Gastrin-Releasing Peptide Receptor Antagonist [99MTc]Tc-Rm26 is a Novel Radiopharmaceutical for Prostate Cancer Imaging. Medical Radiology and Radiation Safety. 2025;70(1):109–114. (In Russian). DOI:10.33266/1024-6177-2025-70-1-109-114
References
1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249.
2. Состояние онкологической помощи населению России в 2022 году / Под ред. А.Д.Каприна, В.В.Старинского, А.О.Шахзадовой. М.: МНИОИ им. П.А.Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2022. 239 с. [Sostoyaniye Onkologicheskoy Pomoshchi Naseleniyu Rossii v 2022 Godu = The State of Oncological Care for the Population of Russia in 2022. Ed. A.D.Kaprin, V.V.Starinskiy, A.O.Shakhzadova. Moscow Publ., 2022. 239 p. (In Russ.)].
3. Miller K.D., Nogueira L., Devasia T., Mariotto A.B., Yabroff K.R., Jemal A., Kramer J., Siegel R.L. Cancer Treatment and Survivorship Statistics. CA Cancer J Clin. 2022;72:409-436. doi: 10.3322/caac.21731.
4. Von Eyben F.E., Picchio M., von Eyben R., Rhee H., Bauman G. 68Ga-Labeled Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis. Eur. Urol. Focus. 2018;4:686–693.
5. Ananias H.J., van den Heuvel M.С., Helfrich W., de Jong I.J. Expression of the Gastrin-Releasing Peptide Receptor, the Prostate Stem Cell Antigen and the Prostate-Specific Membrane Antigen in Lymph Node and Bone Metastases of Prostate Cancer. Prostate. 2009;69:1101–1108.
6. Beer M., Montani M., Gerhardt J., Wild P.J., Hany T.F., Hermanns T., Müntener M., Kristiansen G. Profiling Gastrin-Releasing Peptide Receptor in Prostate Tissues: Clinical Implications and Molecular Correlates. Prostate. 2012;72:318-325.
7. Cornelio D.B., Roesler R., Schwartsmann G. Gastrin-Releasing Peptide Receptor as a Molecular Target in Experimental Anticancer Therapy. Ann Oncol. 2007;18;1457-1466. doi: 10.1093/annonc/mdm058.
8. Dalm S.U., Martens J.W., Sieuwerts A.M., van Deurzen C.H., Koelewijn S.J., de Blois E., Maina T., Nock B.A., Brunel L., Fehrentz J.-A., Martinez J., de Jong M., Melis M. In vitro and in vivo Application of Radiolabeled Gastrin-Releasing Peptide Receptor Ligands in Breast Cancer. J Nucl Med. 2015;56:752-757. doi: 10.2967/jnumed.114.153023.
9. Morgat C., MacGrogan G., Brouste V., Vélasco V., Sévenet N., Bonnefoi H., Fernandez P., Debled M., Hindié E. Expression of Gastrin-Releasing Peptide Receptor in Breast Cancer and Its Association with Pathologic. Biologic. and Clinical Parameters: a Study of 1.432 Primary Tumors. J Nucl Med. 2017;58:1401-1407. doi: 10.2967/jnumed.116.188011.
10. Ceci F., Castellucci P., Polverari G., Iagaru A. Clinical Application of Fluciclovine PET. Choline PET and Gastrin-Releasing Polypeptide Receptor (Bombesin) Targeting PET in Prostate Cancer. Curr Opin Urol. 2020;30:641-648. doi: 10.1097/MOU.0000000000000794.
11. Bodei L., Ferrari M., Nunn A., Llull J., Cremonesi M., Martano L., Laurora G., Scardino E., Tiberini S., Bufi G., Eato de Cobelli O., Paganelli G. 177Lu-AMBA Bombesin Analogue in Hormone Refractory Prostate Cancer Patients: a Phase I Escalation Study with Single-Cycle Administrations [Abstract]. Eur J Nucl Med Mol Imaging. 2007;34;2:221.
12. Schally A.V., Comaru-Schally A.M., Nagy A., Kovacs M., Szepeshazi K., Plonowski A., Varga J.L., Halmos G. Hypothalamic Hormones and Cancer. Front Neuroendocrinol. 2001;22:248–291.
13. Millar J.B.; Rozengurt E. Chronic Desensitization to Bombesin by Progressive Down-Regulation of Bombesin Receptors in Swiss 3T3 cells. Distinction from Acute Desensitization. J Biol Chem. 1990;265:12052–12058.
14. Schwartsmann G., DiLeone L.P., Horowitz M., Schunemann D., Cancella A., Pereira A.S., Richter M., Souza F., da Rocha A.B., Souza F.H., Pohlmann P., De Nucci G. A Phase I Trial of the Bombesin/Gastrin-Releasing Peptide (BN/GRP) Antagonist RC3095 in Patients with Advanced Solid Malignancies. Invest New Drugs. 2006;24:403–412.
15. Mansi R., Nock B.A., Dalm S.U., Busstra M.B., van Weerden W.M., Maina T. Radiolabeled Bombesin Analogs. Cancers (Basel). 2021;13:5766. doi: 10.3390/cancers13225766.
16. Nock B.A., Kaloudi A., Kanellopoulos P., Janota B., Bromińska B., Iżycki D., Mikołajczak R., Czepczynski R., Maina T. [99mTc]Tc-DB15 in GRPR-Targeted Tumor Imaging with SPECT: from Preclinical Evaluation to the First Clinical Outcomes. Cancers (Basel). 2021;13:5093. doi: 10.3390/cancers13205093.
17. Abouzayed A., Rinne S.S., Sabahnoo H., Sörensen J., Chernov V., Tolmachev V., Orlova A. Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists MaSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer. Pharmaceutics. 2021;13:182.
18. Bragina O., Chernov V., Schulga А., Konovalova E., Garbukov E., Vorobyeva A., Orlova A., Tashireva L., Sörensen J., Zelchan R., Medvedeva A., Deyev S., Tolmachev V. Phase I Trial of 99mTc-(HE)3-G3 a DARPin-Based Probe for Imaging of HER2 Expression in Breast Cancer. J Nucl Med. 2022;63:528-535.
19. Schroeder R., de Visser M., van Weerden W.M. Androgen-Regulated Gastrin-Releasing Peptide Receptor Expression in Androgen-Dependent Human Prostate Tumor Xenografts. Int J Cancer. 2010;126;12:2826–2834. doi: 10.1002/ijc.25000.
20. Брагина О.Д., Чернов В.И., Ларькина М.С., Зельчан Р.В., Синилкин И.Г., Медведева А.А. Простатический специфический мембранный антиген: современные возможности в диагностике рака предстательной железы // Молекулярная медицина. 2018. Т.16. №4. С. 3-8 [Bragina O.D., Chernov V.I., Lar’kina M.S., Zel’chan R.V., Sinilkin I.G., Medvedeva A.A. Prostate-Specific Membrane Antigen: Modern Possibilities in the Diagnosis of Prostate Cancer. Molekulyarnaya Meditsina = Molecular Medicine. 2018;16;4:3-8 (In Russ.)].
21. Медведева А.А., Чернов В.И., Усынин Е.А., Зельчан Р.В., Брагина О.Д., Лушникова Н.А. Использование 177Lu-ПСМА для радионуклидной терапии у пациентов с кастрационно-резистентным раком предстательной железы // Сибирский онкологический журнал. 2021. Т.20. №3. С. 115-123 [Medvedeva A.A., Chernov V.I., Usynin Ye.A., Zel’chan R.V., Bragina O.D., Lushnikova N.A. Use of 177Lu-PSMA for Radionuclide Therapy in Patients with Castration-Resistant Prostate Cancer. Sibirskiy Onkologicheskiy Zhurnal = Siberian Journal of Oncology. 2021;20;3:115-123 (In Russ.)]. doi: 10.21294/1814-4861-2021-20-3-115-123
22. Вязьмин В.В., Зуков Р.А., Чанчикова Н.Г., Левченко Е.А., Чернов В.И. Современные возможности ПЭТ/КТ в диагностике рака предстательной железы // Сибирский онкологический журнал. 2021. Т.20. №5. С. 115-122 [Vyaz’min V.V., Zukov R.A., Chanchikova N.G., Levchenko Ye.A., Chernov V.I. Modern Capabilities of PET/CT in the Diagnosis of Prostate Cancer. Sibirskiy Onkologicheskiy Zhurnal = Siberian Oncology Journal. 2021;20;5:115-122 (In Russ.)].
23. Bertacinni G., Impicciatore M., Molina E., Zappia L. Action of Bombesin on Human Gastrointestinal Motility. Italian J Gastroent. 1974;6:45–51.
24. Stoykow C., Erbes T., Maecke H.R., Bulla S., Bartholomä M., Mayer S., Drendel V., Bronsert P., Werner M., Gitsch G., Weber W.A., Stickeler E., Meyer P.T. Gastrin-Releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist 68Ga-RM2 And PET. Theranostics. 2016;6:1641-1650.
25. Wieser G., Mansi R., Grosu A.L., Schultze-Seemann W., Dumont-Walter R.A., Meyer P.T., Maecke H.R., Reubi J.C., Weber W.A. Positron Emission Tomography (PET) Imaging of Prostate Cancer with a Gastrin Releasing Peptide Receptor Antagonist – from Mice to Men. Theranostics. 2014;4:412-419.
26. Kwee S.A., Wei H., Sesterhenn I., Yun D., Coel M.N. Localization of Primary Prostate Cancer with Dual-Phase 18F-Fluorocholine PET. J Nucl Med. 2006;47:262-269.
27. Van de Wiele C., Dumont F., Dierckx R.A., Peers S.H., Thornback J.R., Slegers G., Thierens H. Biodistribution and Dosimetry of 99mTc-RP527 a Gastrin-Releasing Peptide (GRP) Agonist for the Visualization of GRP Receptor–Expressing Malignancies. J Nucl Med. 2001;42:1722–1727.
28. Mather S.J., Nock B.A., Maina T., Gibson V., Ellison D., Murray I., Sobnack R., Colebrook S., Wan S., Halberrt C., Szysko T., Powles T., Avril N. GRP Receptor Imaging of Prostate Cancer Using [99mTc]Demobesin 4: a First-in-Man Study. Mol Imaging Biol. 2014;16:888-895.
29. Bakker I.L., Fröberg A.C., Busstra M.B., Verzijlbergen J.F., Konijnenberg M., van Leenders G.H., Schoots I.G., de Blois E., van Weerden W.M., Dalm S.U., Maina T., Nock B.A., de Jong M. GRPr Antagonist 68Ga-SB3 PET/CT Imaging of Primary Prostate Cancer in Therapy-Naïve Patients. J Nucl Med. 2021;62:1517–1523.
30. Zhang J., Niu G., Fan X., Lang L., Hou G., Chen L., Wu H., Zhu Z., Li F., Chen X. PET Using a GRPR Antagonist 68Ga-RM26 in Healthy Volunteers and Prostate Cancer Patients. J Nucl Med. 2018;59:922–928.
31. den Wyngaert T.V., Elvas F., De Schepper S., Kennedy J.A., Israel O. SPECT/CT: Standing on the Shoulders of Giants. It is Time to Reach for the Sky! J Nucl Med. 2020;61:1284–1291.
32. Chernov V., Rybina A., Zelchan R., Medvedeva A., Bragina O., Lushnikova N., Doroshenko A., Usynin E., Tashirevа L., Vtorushin S., Abouzayed A., Rinne S.S., Sörensen J., Tolmachev V., Orlova A. Phase I Trial of [99m Tc]Tc-maSSS-PEG2 -RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors. Cancers. 2023;15:1631. doi: 10.3390/cancers15061631.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. With the support of the Strategic Academic Leadership program ‟Priority 2030” No. 2030-FROM-024-202–2024 ‟Radionuclide theranostics of prostate cancer”.
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.10.2024. Accepted for publication: 25.11.2024.