99mTc-Labelled Low Molecular Weight Inhibitors of Prostate-specific Membrane Antigen



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

High morbidity and mortality rates of prostate cancer (PCa) determine the requirement of looking for new methods of its early diagnosis. Methods of nuclear medicine have a special place in addressing this problem as they allow functional, metabolic and other processes imaging in body, which occur during the cancer development. This approach supposes the use of radiopharmaceuticals (RP), which are capable of selective binding to a specific biological target, for example, prostate-specific membrane antigen (PSMA), which is known to be overexpressed in PCa. Current development of new radiotracers for PCa imaging is focused on low molecular weight PSMA inhibitors due to their high specific binding to PSMA and rapid urinary excretion. Technetium-99m remains the appropriate radionuclide for diagnostic studies due to its optimal nuclear properties, ease of production and versatile coordination chemistry. Therefore, SPECT imaging with 99mTc-PSMA radioligands can be a cost effective alternative to PET with 68Ga- or 18F-labeled RP. The aim of this review is to summarize and analyze currently available data on 99mTc-labeled low molecular weight PSMA inhibitors for metastatic PCa imaging

Full Text

Restricted Access

About the authors

Oxana Petrovna Vlasova

National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: somina@inbox.ru
ORCID iD: 0000-0001-5170-9595
SPIN-code: 2554-3985

PhD in Biology, Leading Researcher, Laboratory of Experimental Nuclear Medicine

Russian Federation, 4 Korolyova str., Obninsk, Kaluga Region, 249036, Russia

Viktoriia Konstantinovna Tishchenko

A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russia

Email: vikshir82@mail.ru
ORCID iD: 0000-0001-8983-5976
SPIN-code: 2724-0930

MD, PhD, Leading Researcher at the Laboratory of Experimental Nuclear Medicine

Russian Federation, 4 Korolyova str., Obninsk, Kaluga Region, 249036, Russia

Vasily Mihailovich Petriev

A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russia;
National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia

Email: petriev@mrrc.obninsk.ru
ORCID iD: 0000-0002-0231-2177
SPIN-code: 3769-6210

MD, PhD, Head of the Laboratory Experimental Nuclear Medicine

Russian Federation, 4 Korolyova str., Obninsk, Kaluga Region, 249036, Russia; 31 Kachira str., Moscow, 115409, Russia

Andrei Alexandrovich Pankratov

P.A. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Moscow, Russia

Email: andreimnioi@yandex.ru
ORCID iD: 0000-0001-7291-9743
SPIN-code: 5463-3790

PhD, Head of the Department of Pathomorphology

Russian Federation, 3 2nd Botkinskiy proezd, Moscow, 125284, Russia

Natalia Borisovna Morozova

P.A. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Moscow, Russia

Email: n.b.morozova@yandex.ru
ORCID iD: 0000-0002-7159-805X
SPIN-code: 1286-6518

leading researcher of the Department of Pathomorphology

Russian Federation, 3 2nd Botkinskiy proezd, Moscow, 125284, Russia

Petr Viktorovich Shegai

National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russia

Email: dr.shegai@mail.ru
ORCID iD: 0000-0001-8901-4596
SPIN-code: 6849-3221

Deputy Director General for Science

Russian Federation, 4 Korolyova str., Obninsk, Kaluga Region, 249036, Russia

Sergei Anatolievich Ivanov

A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russia

Email: oncourolog@gmail.com
ORCID iD: 0000-0001-7689-6032
SPIN-code: 4264-5167

Director

Russian Federation, 4 Korolyova str., Obninsk, Kaluga Region, 249036, Russia

Andrei Dmitrievich Kaprin

National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russia

Email: kaprin@mail.ru
ORCID iD: 0000-0001-8784-8415
SPIN-code: 1759-8101

 
 
Russian Federation, 4 Korolyova str., Obninsk, Kaluga Region, 249036, Russia

References

  1. Global Cancer Observatory. Accessed April 12, 2022. https://gco.iarc.fr.
  2. Состояние онкологической помощи населению России в 2020 году / под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2021. 239 с.
  3. Mottet N, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021;79(2):243–262. doi: 10.1016/j.eururo.2020.09.042.
  4. Xu X, Zhang J, Hu S, et al. 99m Tc-labeling and evaluation of a HYNIC modified small-molecular inhibitor of prostate-specific membrane antigen. Nucl Med Biol. 2017;48:69–75. doi: 10.1016/j.nucmedbio.2017.01.010.
  5. Walker SM, Lim I, Lindenberg L, et al. Positron emission tomography (PET) radiotracers for prostate cancer imaging. Abdom Radiol (NY). 2020;45(7):2165–2175. doi: 10.3390/ijms23095023.
  6. Stott Reynolds TJ, Smith CJ, Lewis MR. Peptide-Based Radiopharmaceuticals for Molecular Imaging of Prostate Cancer. Adv Exp Med Biol. 2018;1096:135–158. doi: 10.1007/978-3-319-99286-0_8.
  7. Kuppermann D, Calais J, Marks LS. Imaging Prostate Cancer: Clinical Utility of Prostate-Specific Membrane Antigen. J Urol. 2022;27:769–778. doi: 10.1097/JU.0000000000002457.
  8. Леонтьев А.В., Халимон А.И., Кулиев М.Т., и др. Современные возможности применения радио¬фармпрепаратов на основе лигандов к простатспецифическому мембранному антигену, меченных 99mTc, при раке предстательной железы // Онкоурология. – 2021. – Т. 17. – № 4. – С. 136–50. [Leontyev AV, Khalimon AI, Kuliev MT, et al. Modern possibilities of application 99mTc-labeled prostate-specific membrane antigen ligands in prostate cancer. Onkourologiya = Cancer Urology. 2021;17(4):136–50. (In Russ.).]. doi: 10.17650/1726-9776-2021-17-4-136-150.
  9. Duatti A. Review on 99mTc radiopharmaceuticals with emphasis on new advancements. Nucl Med Biol. 2021;92:202–216. doi: 10.1016/j.nucmedbio.2020.05.005.
  10. Gourni E, Henriksen G. Metal-Based PSMA Radioligands. Molecules. 2017;22(4):523. doi: 10.3390/molecules22040523.
  11. Brunello S., Salvarese N, Carpanese D, et al. A Review on the Current State and Future Perspectives of [99mTc]Tc-Housed PSMA-i in Prostate Cancer. Molecules. 2022;27(9):2617. doi: 10.3390/molecules27092617.
  12. Czerwińska M, Bilewicz A, Kruszewski M, et al. Targeted Radionuclide Therapy of Prostate Cancer – From Basic Research to Clinical Perspectives. Molecules. 2020;25(7):1743. doi: 10.3390/molecules25071743.
  13. Mattias J, Engelhardt J, Schäfer M, et al. Cytoplasmic Localization of Prostate-Specific Membrane Antigen Inhibitors May Confer Advantages for Targeted Cancer Therapies. Cancer Res. 2021;81(8):2234–2245. doi: 10.1158/0008-5472.CAN-20-1624.
  14. Kopka K, Benešova M, Barinka C, et al. Glu-Ureido-Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic Radiotracers. J Nucl Med. 2017;58(Suppl 2):17S–26S. doi: 10.2967/jnumed.116.186775.
  15. Марук А.Я., Брускин А.Б., Кодина Г.Е. Новые радиофармпрепараты на основе 99mTc с применением бифункциональных хелатирующих агентов // Радиохимия. – 2011. – Т. 53. – № 4. – С. 289–300. [Maruk AYa, Bruskin AB, Kodina GE. Novel 99mTc radiopharmaceuticals with bifunctional chelating agents. Radiochemistry. 2011;53(4):341–353.] doi: 10.1134/S1066362211040011.
  16. Banerjee SR, Foss CA, Castanares M, et al. Synthesis and Evaluation of Technetium-99m- and Rhenium-Labeled Inhibitors of the Prostate-Specific Membrane Antigen (PSMA). J Med Chem. 2008;51(15):4504–4517. doi: 10.1021/jm800111u.
  17. Banerjee SR, Pullambhatla M, Foss CA, et al. Effect of Chelators on the Pharmacokinetics of 99mTc-Labeled Imaging Agents for the Prostate-Specific Membrane Antigen (PSMA). J Med Chem. 2013;56(15):6108–6121. doi: 10.1021/jm400823w.
  18. Lu G, Maresca KP, Hillier SM, et al. Synthesis and SAR of 99mTc/Re-Labeled Small Molecule Prostate Specific Membrane Antigen Inhibitors with Novel Polar Chelates. Bioorg Med Chem Lett. 2013;23(5):1557–1563. doi: 10.1016/j.bmcl.2012.09.014.
  19. Hillier SM, Maresca KP, Lu G, et al. 99mTc-Labeled Small-Molecule Inhibitors of Prostate-Specific Membrane Antigen for Molecular Imaging of Prostate Cancer. J Nucl Med. 2013;54:1369–1376. doi: 10.2967/jnumed.112.116624.
  20. Kimura H, Sampei S, Matsuoka D, et al. Development of 99mTc-labeled asymmetric urea derivatives that target prostate-specific membrane antigen for single-photon emission computed tomography imaging. Bioorg Med Chem. 2016;24(10):2251–2256. doi: 10.1016/j.bmc.2016.03.051.
  21. Lodhi NA, Park JY, Kim K, et al. Synthesis and Evaluation of 99mTc-Tricarbonyl Labeled Isonitrile Conjugates for Prostate-Specific Membrane Antigen (PSMA) Image. Inorganics. 2020;8(1):5. doi: 10.3390/inorganics8010005.
  22. Xiao D, Duan X, Gan Q, et al. Preparation and Biological Evaluation of [ 99m Tc]Tc-CNGU as a PSMA-Targeted Radiotracer for the Imaging of Prostate Cancer. Molecules. 2020;25:5548. doi: 10.3390/molecules25235548.
  23. Kularatne SA, Zhou Z, Yang J, et al. Design, Synthesis, and Preclinical Evaluation of Prostate-Specific Membrane Antigen Targeted 99mTc-Radioimaging Agents. Mol Pharm. 2009;6(3):790–800. doi: 10.1021/mp9000712.
  24. Robu S, Schottelius M, Eiber M, et al. Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer. J Nucl Med. 2017;58(2):235–242. doi: 10.2967/jnumed.116.178939.
  25. Rauscher I, Duwel C, Wirtz M, et al. Value of (111) In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: Correlation with histopathology and clinical follow-up. BJU Int. 2017;120(1):40–47. doi: 10.1111/bju.13713.
  26. Jilg CA, Reichel K, Stoykow C, et al. Results from extended lymphadenectomies with [(111)In]PSMA-617 for intraoperative detection of PSMA-PET/CT-positive nodal metastatic prostate cancer. EJNMMI Res. 2020;10(1):17. doi: 10.1186/s13550-020-0598-2.
  27. Ferro-Flores G, Luna-Gutierrez M, Ocampo-Garcia B, et al. Clinical translation of a PSMA inhibitor for 99m Tc-based SPECT. Nucl Med Biol. 2017;48:36–44. doi: 10.1016/j.nucmedbio.2017.01.012.
  28. Mosayebnia M, Hajimahdi Z, Beiki D, et al. Design, Synthesis, Radiolabeling and Biological Evaluation of New Urea-Based Peptides Targeting Prostate Specific Membrane Antigen. Bioorg Chem. 2020;99:103743. doi: 10.1016/j.bioorg.2020.103743.
  29. Sikora AE, Maurin M, Jaron AW, et al. PSMA Inhibitor Derivatives for Labelling with 99mTc via HYNIC, a Radiopharmaceutical Kit, Radiopharmaceutical Preparations and Their Use in Prostate Cancer Diagnostics. Bulletin Number EP3721907A1. European Patent; 2020.
  30. Vats K, Agrawal K, Sharma R, et al. Preparation and clinical translation of 99m Tc-PSMA-11 for SPECT imaging of prostate cancer. Medchemcomm. 2019;10(12):2111–2117. doi: 10.1039/c9md00401g.
  31. Vallabhajosula S, Nikolopoulou A, Babich JW, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen: pharmacokinetics and biodistribution studies in healthy subjects and patients with metastatic prostate cancer. J Nucl Med. 2014;55(11):1791–1798. doi: 10.2967/jnumed.114.140426.
  32. Goffin KE, Joniau S, Tenke P, et al. Phase 2 study of 99mTc-Trofolastat SPECT/CT to identify and localize prostate cancer in intermediate-and high-risk patients undergoing radical prostatectomy and extended pelvic LN dissection. J Nucl Med. 2017;58(9):1408– 1413. doi: 10.2967/jnumed.116.187807.
  33. Schmidkonz C, Cordes M, Beck M, et al. SPECT/CT With the PSMA Ligand 99mTc-MIP-1404 for Whole-Body Primary Staging of Patients With Prostate Cancer. Clin Nucl Med. 2018;43(4):225–231. doi: 10.1097/RLU.0000000000001991.
  34. Schmidkonz C, Atzinger A, Goetz TI, et al. 99mTc-MIP-1404 SPECT/CT for Patients With Metastatic Prostate Cancer: Interobserver and Intraobserver Variability in Treatment-Related Longitudinal Tracer Uptake Assessments of Prostate-Specific Membrane Antigen-Positive Lesions. Clin Nucl Med. 2020;45(2):105–112. doi: 10.1097/RLU.0000000000002880.
  35. Schmidkonz C, Hollweg C, Beck M, et al. 99mTc-MIP-1404-SPECT/CT for the Detection of PSMA-Positive Lesions in 225 Patients with Biochemical Recurrence of Prostate Cancer. Prostate. 2018;78(1):54–63. doi: 10.1002/pros.23444.
  36. Reinfelder J, Kuwert T, Beck M, et al. First Experience with SPECT/CT Using a 99mTc-Labeled Inhibitor for Prostate-Specific Membrane Antigen in Patients with Biochemical Recurrence of Prostate Cancer. Clin Nucl Med. 2017;42(1):26–33. doi: 10.1097/RLU.0000000000001433.
  37. Schmidkonz C, Götz TI, Atzinger A, et al. 99mTc-MIP-1404 SPECT/CT for Assessment of Whole-Body Tumor Burden and Treatment Response in Patients With Biochemical Recurrence of Prostate Cancer. Clin Nucl Med. 2020;45(8):e349–e357. doi: 10.1097/RLU.0000000000003102.
  38. Schmidkonz C, Goetz TI, Kuwert T, et al. PSMA SPECT/CT with 99mTc-MIP-1404 in Biochemical Recurrence of Prostate Cancer: Predictive Factors and Efficacy for the Detection of PSMA-Positive Lesions at Low and Very-Low PSA Levels. Ann Nucl Med. 2019;33(12):891–898. doi: 10.1007/s12149-019-01400-6.
  39. Schmidkonz C, Cordes M, Beck M, et al. Assessment of Treatment Response by 99mTc-MIP-1404 SPECT/CT: A Pilot Study in Patients With Metastatic Prostate Cancer. Clin Nucl Med. 2018;43(8):e250–e258. doi: 10.1097/RLU.0000000000002162.
  40. Ellis WJ, Donnelly BJ, Gorin MA, et al. A phase study to evaluate the safety and efficacy of 99mTc-MIP-1404 SPECT/CT imaging to detect clinically significant prostate cancer in men with biopsy proven low grade prostate cancer who are candidates for active surveillance (PROSPECT-AS). J Urol. 2019;201(Suppl4):e1100. doi.org/10.1097/01.JU.0000557222.99762.6b.
  41. Maurer T, Robu S, Schottelius M, et al. 99m Technetium-based Prostate-specific Membrane Antigen-radioguided Surgery in Recurrent Prostate Cancer. Eur Urol. 2019;75(4):659–666. doi: 10.1016/j.eururo.2018.03.013.
  42. Mix M, Schultze-Seemann W, von Büren M, et al. 99mTc-Labelled PSMA Ligand for Radio-Guided Surgery in Nodal Metastatic Prostate Cancer: Proof of Principle. EJNMMI Res. 2021;11(1):22. doi: 10.1186/s13550-021-00762-1.
  43. Horn T, Kronke M, Rauscher I, et al. Single Lesion on Prostate-specific Membrane Antigen-ligand Positron Emission Tomography and Low Prostate-specific Antigen Are Prognostic Factors for a Favorable Biochemical Response to Prostate-specific Membrane Antigen-targeted Radioguided Surgery in Recurrent Prostate Cancer. Eur Urol. 2019;76(4):517–523. doi: 10.1016/j.eururo.2019.03.045.
  44. Werner P, Neumann C, Eiber M, et al. [(99cm)Tc]Tc-PSMA-I&S-SPECT/CT: Experience in prostate cancer imaging in an outpatient center. EJNMMI Res. 2020;10(1):45. doi: 10.1186/s13550-020-00635-z.
  45. Albalooshi B, Al Sharhan M, Bagheri F, et al. Direct Comparison of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT in Patients with Prostate Cancer. Asia Ocean J Nucl Med Biol. 2020;8:1–7. doi: 10.22038/aojnmb.2019.43943.1293.
  46. Urbán S, Meyer C, Dahlbom M, et al. Radiation Dosimetry of (99m)Tc-PSMA I&S: A Single-Center Prospective Study. J Nucl Med. 2021;62(8):1075–1081. doi: 10.2967/jnumed.120.253476.
  47. Santos-Cuevas C, Davanzo J, Ferro-Flores G, et al. 99m Tc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients. Nucl Med Biol. 2017;52:1–6. doi: 10.1016/j.nucmedbio.2017.05.005.
  48. Lawal IO, Ankrah AO, Mokgoro NP, et al. Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: a comparative analysis with Ga-68 PSMA PET/CT. Prostate. 2017;77(11):1205–12. doi: 10.1002/pros.23379.
  49. García-Pérez FO, Davanzo J, López-Buenrostro S, et al. Head to Head Comparison Performance of 99mTc-EDDA/HYNIC-IPSMA SPECT/CT and 68Ga-PSMA-11 PET/CT a Prospective Study in Biochemical Recurrence Prostate Cancer Patients. Am J Nucl Med Mol Imaging. 2018;8(5):332–340.
  50. Fallahi B, Khademi N, Karamzade-Ziarati N, et al. 99mTc-PSMA SPECT/CT Versus 68Ga-PSMA PET/CT in the Evaluation of Metastatic Prostate Cancer. Clin Nucl Med. 2021;46(2):e68. doi: 10.1097/RLU.0000000000003410.
  51. Kabunda J, Gabela L, Kalinda C, et al. Comparing 99mTc-PSMA to 99mTc-MDP in Prostate Cancer Staging of the Skeletal System. Clin Nucl Med. 2021;46(7):562–568. doi: 10.1097/RLU.0000000000003702.
  52. Vallejo-Armenta P, Soto-Andonaegui J, Villanueva-Pérez RM, et al. [99mTc]Tc-IPSMA SPECT Brain Imaging as a Potential Specific Diagnosis of Metastatic Brain Tumors and High-Grade Gliomas. Nucl Med Biol. 2021;96–97:1–8. doi: 10.1016/j.nucmedbio.2021.02.003.
  53. Liu C, Zhu Y, Su H, et al. Relationship between PSA Kinetics and Tc-99m HYNIC PSMA SPECT/CT Detection Rates of Biochemical Recurrence in Patients with Prostate Cancer after Radical Prostatectomy. Prostate. 2018;78(16):1215–1221. doi: 10.1002/pros.23696.
  54. Su HC, Zhu Y, Ling GW, et al. Evaluation of 99mTc-Labeled PSMA-SPECT/CT Imaging in Prostate Cancer Patients Who Have Undergone Biochemical Relapse. Asian J Androl. 2017;19(3):267–271. doi: 10.4103/1008-682X.192638.
  55. Su H, Zhu Y, Hu S, et al. The Value of 99mTc-PSMA SPECT/CT-Guided Surgery for Identifying and Locating Lymph Node Metastasis in Prostate Cancer Patients. Ann Surg Oncol. 2019;26:653–659. doi: 10.1245/s10434-018-6805-y.
  56. Li P, Liu C, Wu S, et al. Combination of 99mTc-Labeled PSMA-SPECT/CT and Diffusion-Weighted MRI in the Prediction of Early Response After Carbon Ion Therapy in Prostate Cancer: A Non-Randomized Prospective Pilot Study. Cancer Manag Res. 2021;13:2191–2199. doi: 10.2147/CMAR.S285167.
  57. Ćwikła JB, Roslan M, Skoneczna I, et al. Initial Experience of Clinical Use of [99mTc]Tc-PSMA-T4 in Patients with Prostate Cancer. A Pilot Study. Pharmaceuticals (Basel). 2021;14(11):1107. doi: 10.3390/ph14111107.
  58. Sergieva S, Mangaldgiev R, Dimcheva M, et al. SPECT-CT Imaging with [99mTc]PSMA-T4 in patients with Recurrent Prostate Cancer. Nucl Med Rev Cent East Eur. 2021;24(2):70–81. doi: 10.5603/NMR.2021.0018.
  59. Singh B, Sharma S, Bansal P, et al. Comparison of the Diagnostic Utility of 99mTc-PSMA Scintigraphy versus 68Ga-PSMA-11 PET/CT in the Detection of Metastatic Prostate Cancer and Dosimetry Analysis: A Gamma-Camera-Based Alternate Prostate-Specific Membrane Antigen Imaging Modality. Nucl Med Commun. 2021;42:482–489. doi: 10.1097/MNM.0000000000001361.)

Supplementary files

There are no supplementary files to display.


Copyright (c) "Paediatrician" Publishers LLC



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies