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PSMA Inhibitors for Nuclear Imaging and Radiotherapy of Prostate Cancer

  • Sajid Mushtaq (Department of Nuclear Engineering, Pakistan Institute of Engineering and Applied Sciences) ;
  • Tugsuu Uyanga (Nuclear Medicine Department,National Diagnostic and Treatment Center (NDTC), Second State Central Hospital) ;
  • Park Ji Ae (Division of Applied RI, Korea Institute of Radiological & Medical Sciences (KIRAMS)) ;
  • Jung Young Kim (Division of Applied RI, Korea Institute of Radiological & Medical Sciences (KIRAMS))
  • Received : 2023.04.07
  • Accepted : 2023.05.12
  • Published : 2023.06.30

Abstract

Prostate cancer ranks as the world's second most frequently diagnosed cancer among men, and is responsible for the fifth highest number of cancer-related deaths in this population. The development of effective diagnostic and therapeutic approaches for prostate cancer remains a major challenge in the field of oncology. Over the past few years, the prostate-specific membrane antigen (PSMA) has raised as a hopeful tracer for the diagnosis and treatment of prostate cancer.Various radioisotopes, such as 131I, 99mTc, 68Ga, and 177Lu, have been used to label PSMA analogues, with varying degrees of success. Among these, 68Ga-PSMA-11 and 177Lu-PSMA-617 have emerged as the most promising radioligands for clinical use. Recently, researchers have been exploring the use of other radioisotopes, such as 211At, 89Zr, 64/67Cu, and 203/212Pb, for the labeling of PSMA-targeted radioligands. These radioisotopes have unique properties that may offer advantages over existing radioligands, such as longer half-lives, higher specific activities, and different emission profiles. Efforts are currently underway to develop these radiopharmaceuticals and make them more widely available for clinical use. These exciting developments highlight the potential of PSMA-targeted radioligands for the diagnosis and treatment of prostate cancer, and provided significant implications for the management of this disease in the future. The current study aims to provide a comprehensive summary of the latest research and clinical applications of radiolabeled PSMA inhibitors for diagnoses and therapy of prostate cancer, emphasizing the exciting developments in the field and their potential impact on clinical practice.

Keywords

Acknowledgement

This work was supported by a grant of the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by MSIT, Republic of Korea (No. 50461-2023).

References

  1. Boettcher AN, Usman A, Morgans A, VanderWeele DJ, Sosman J, Wu JD. Past, current, and future of immunotherapies for prostate cancer. Front Oncol 2019;9:884.
  2. Moschini M, Zaffuto E, Karakiewicz PI, Andrea DD, Foerster B, Abufaraj M, Soria F, Mattei A, Montorsi F, Briganti A, Shariat SF. External beam radiotherapy increases the risk of bladder cancer when compared with radical prostatectomy in patients affected by prostate cancer: a population-based analysis. Eur Urol 2019;75(2):319-28. https://doi.org/10.1016/j.eururo.2018.09.034
  3. Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. Jama 2005; 294(2):238-44. https://doi.org/10.1001/jama.294.2.238
  4. Crawford ED, Higano CS, Shore ND, Hussain M, Petrylak DP. Treating patients with metastatic castration resistant prostate cancer: a comprehensive review of available therapies. J Urol 2015;194(6):1537-47. https://doi.org/10.1016/j.juro.2015.06.106
  5. Ingrosso G, Detti B, Scartoni D, Lancia A, Giacomelli I, Baki M, Carta G, Livi L, Santoni R. Current therapeutic options in metastatic castration-resistant prostate cancer. Semin Oncol 2018;45(5-6):303-15. https://doi.org/10.1053/j.seminoncol.2018.10.001
  6. Nizialek E, Antonarakis ES. PARP inhibitors in metastatic prostate cancer: evidence to date. Cancer Manag Res 2020;12:8105.
  7. Wustemann T, Haberkorn U, Babich J, Mier W. Targeting prostate cancer: Prostate-specific membrane antigen based diagnosis and therapy. Med Res Rev 2019;39(1):40-69. https://doi.org/10.1002/med.21508
  8. Kinoshita Y, Kuratsukuri K, Landas S, Imaida K, Rovito PM, Wang CY, Haas GP. Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J. Surg 2006;30:628-36. https://doi.org/10.1007/s00268-005-0544-5
  9. Cimadamore A, Cheng M, Santoni M, Lopez-Beltran A, Battelli N, Massari F, Galosi AB, Scarpelli M, Montironi R. New prostate cancer targets for diagnosis, imaging, and therapy: Focus on prostate-specific membrane antigen. Front Oncol 2018;8:653.
  10. Wang F, Li Z, Feng X, Yang D, Lin M. Advances in PSMA-targeted therapy for prostate cancer. Prostate Cancer Prostatic Dis 2022;25(1):11-26. https://doi.org/10.1038/s41391-021-00394-5
  11. Deegen P, Thomas O, Nolan-Stevaux O, Li S, Wahl J, Bogner P, Aeffner F, Friedrich M, Liao MZ, Matthes K, Rau D. The PSMA-targeting Half-life Extended BiTE Therapy AMG 160 has Potent Antitumor Activity in Preclinical Models of Metastatic Castration-resistant Prostate Cancer Preclinical Evaluation of AMG 160 in mCRPC Models. Clin Cancer Res 2021;27(10):2928-37. https://doi.org/10.1158/1078-0432.CCR-20-3725
  12. Pomper MG, Musachio JL, Zhang J, Scheffel U, Zhou Y, Hilton J, Maini A, Dannals RF, Wong DF, Kozikowski AP. 11C-MCG: synthesis, uptake selectivity, and primate PET of a probe for glutamate carboxypeptidase II (NAALADase). Mol Imaging 2002;1(2):96-101. https://doi.org/10.1162/153535002320162750
  13. Chen Y, Pullambhatla M, Foss CA, Byun Y, Nimmagadda S, Senthamizhchelvan S, Sgouros G, Mease RC, Pomper MG. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F] DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Clin Cancer Res 2011;17(24):7645-53. https://doi.org/10.1158/1078-0432.CCR-11-1357
  14. Eder M, Schafer M, Bauder-Wust U, Hull WE, Wangler C, Mier W, Haberkorn U, Eisenhut M. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 2012;23(4):688-97. https://doi.org/10.1021/bc200279b
  15. Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, Holland-Letz T, Hadaschik BA, Giesel FL, Debus J, Haberkorn U. Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2014;41:11-20. https://doi.org/10.1007/s00259-013-2525-5
  16. Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, Hruby G, Fogarty G, Jagavkar R, Kneebone A, Hickey A, Fanti S, Tarlinton L, Emmett L. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med 2015;56(8):1185-90. https://doi.org/10.2967/jnumed.115.160382
  17. Evans MJ, Smith-Jones PM, Wongvipat J, Navarro V, Kim S, Bander NH, Larson SM, Sawyers CL. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc Natl Acad Sci U S A 2011;108(23):9578-82. https://doi.org/10.1073/pnas.1106383108
  18. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Graner FP, Kubler H, Haberkorn U, Eisenhut M, Wester HJ, Gschwend JE, SchwaigerM. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 2015;56(5):668-74. https://doi.org/10.2967/jnumed.115.154153
  19. Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, Debus N, Eder M, Eisenhut M, Schafer M, Neels O, Hohenfellner M, Kopka K, Kauczor HU, Debus J, Haberkorn U. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging 2017;44(8):1258-68. https://doi.org/10.1007/s00259-017-3711-7
  20. Afshar-Oromieh A, Haberkorn U, Schlemmer HP, Fenchel M, Eder M, Eisenhut M, Hadaschik BA, Kopp-Schneider A, Rothke M. Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur J Nucl Med Mol Imaging 2014;41(5):887-97. https://doi.org/10.1007/s00259-013-2660-z
  21. Maresca KP, Hillier SM, Femia FJ, Keith D, Barone C, Joyal JL, Zimmerman CN, Kozikowski AP, Barrett JA, Eckelman WC, Babich JW. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J Med Chem 2009;52(2):347-57. https://doi.org/10.1021/jm800994j
  22. Hillier SM, Maresca KP, Femia FJ, Marquis JC, Foss CA, Nguyen N, Zimmerman CN, Barrett JA, Eckelman WC, Pomper MG, Joyal JL, Babich JW. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res 2009;69(17):6932-40. https://doi.org/10.1158/0008-5472.CAN-09-1682
  23. Barrett JA, Coleman RE, Goldsmith SJ, Vallabhajosula S, Petry NA, Cho S, Armor T, Stubbs JB, Maresca KP, Stabin MG, Joyal JL,Eckelman WC, BabichJW. First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer. J Nucl Med 2013;54(3):380-7. https://doi.org/10.2967/jnumed.112.111203
  24. Hillier SM, Kern AM, Maresca KP, Marquis JC, Eckelman WC, Joyal JL, Babich JW. 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy. J Nucl Med 2011;52(7): 1087-93. https://doi.org/10.2967/jnumed.110.086751
  25. Hillier S, Rubino K, Maresca K, Marquis J, Tesson M, Zimmerman C, Eckelman W, Mairs R, Joyal J, Babich J. [131I] MIP-1466, a small molecule prostate-specific membrane antigen (PSMA) inhibitor for targeted radiotherapy of prostate cancer (PCa). J Nucl Med 2012;53(1):170.
  26. Zechmann CM, Afshar-Oromieh A, Armor T, Stubbs JB, Mier W, Hadaschik B, Joyal J, Kopka K, Debus J, Babich JW, Haberkorn U. Radiation dosimetry and first therapy results with a 124I/131I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging 2014;41(7):1280-92. https://doi.org/10.1007/s00259-014-2713-y
  27. Lu G, Maresca KP, Hillier SM, Zimmerman CN, Eckelman WC, Joyal JL, Babich JW. Synthesis and SAR of 99mTc/Re-labeled small molecule prostate specific membrane antigen inhibitors with novel polar chelates. Bioorganic Med Chem Lett 2013;23(5):1557-63. https://doi.org/10.1016/j.bmcl.2012.09.014
  28. Reinfelder J, Kuwert T, Beck M, Sanders JC, Ritt P, Schmidkonz C, Hennig P, Prante O, Uder M, Wullich B, Goebell P. 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. https://doi.org/10.1097/RLU.0000000000001433
  29. Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov 2020;19(9):589-608. https://doi.org/10.1038/s41573-020-0073-9
  30. Khreish F, Ebert N, Ries M, Maus S, Rosar F, Bohnenberger H, Stemler T, Saar M, Bartholoma M, Ezziddin S. 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience. Eur J Nucl Med Mol Imaging 2020;47(3):721-8. https://doi.org/10.1007/s00259-019-04612-0
  31. Khawar A, Eppard E, Sinnes JP, Roesch F, Ahmadzadehfar H, Kurpig S, Meisenheimer M, Gaertner FC, Essler M, Bundschuh RA. Prediction of normal organ absorbed doses for [177Lu]Lu-PSMA-617 using [44Sc]Sc-PSMA-617 pharmacokinetics in patients with metastatic castration resistant prostate carcinoma. Clin Nucl Med 2018;43(7):486-91. https://doi.org/10.1097/RLU.0000000000002102
  32. Benesova M, Schafer M, Bauder-Wust U, Afshar-Oromieh A, Kratochwil C, Mier W, Haberkorn U, Kopka K, Eder M. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 2015;56(6):914-20. https://doi.org/10.2967/jnumed.114.147413
  33. Kasbollah A, Eu P, Cowell S, Deb P. Review on production of 89Zr in a medical cyclotron for PET radiopharmaceuticals. J Nucl Med Technol 2013;41(1):35-41. https://doi.org/10.2967/jnmt.112.111377
  34. Vazquez SM, Endepols H, Fischer T, Tawadros SG, Hohberg M, Zimmermanns B, Dietlein F, Neumaier B, Drzezga A, Dietlein M, Schomacker K. Translational development of a Zr-89-labeled inhibitor of prostate-specific membrane antigen for PET imaging in prostate cancer. Mol Imaging Biol 2022;24(1):115-25. https://doi.org/10.1007/s11307-021-01632-x
  35. Schafer M, Bauder-Wust U, Leotta K, Zoller F, Mier W, Haberkorn U, Eisenhut M, Eder M. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res 2012;2(1):23.
  36. Zalutsky MR, Zhao XG, Alston KL, Bigner D. High-level production of α-particle-emitting 211At and preparation of 211At-labeled antibodies for clinical use. J Nucl Med 2001;42(10):1508-15.
  37. Kiess AP, Minn IL, Vaidyanathan G, Hobbs RF, Josefsson A, Shen C, Brummet M, Chen Y, Choi J, Koumarianou E, Baidoo K, Brechbiel MW, Mease RC,Sgouros G, Zalutsky MR, Pomper MG. (2S)-2-(3-(1-Carboxy-5-(4-211At-astatobenzamido)pentyl)ureido)-pentanedioic acid for PSMA-targeted α-particle radiopharmaceutical therapy. J Nucl Med 2016;57(10):1569-75. https://doi.org/10.2967/jnumed.116.174300
  38. Kelly JM, Amor-Coarasa A, Nikolopoulou A, Wustemann T, Barelli P, Kim D, Williams C, Zheng X, Bi C, Hu B, Warren JD, Hage DS, DiMagno SG, Babich JW. Dual-target binding ligands with modulated pharmacokinetics for endoradiotherapy of prostate cancer. J Nucl Med 2017;58(9):1442-9. https://doi.org/10.2967/jnumed.116.188722
  39. Mease RC, Kang CM, Kumar V, Banerjee SR, Minn IL, Brummet M, Gabrielson KL, Feng Y, Park A, Kiess AP, Sgouros G, Vaidyanathan G, Zalutsky MR, Pomper MG. An improved 211At-labeled agent for PSMA-targeted α-therapy. J Nucl Med 2022;63(2): 259-67. https://doi.org/10.2967/jnumed.121.262098
  40. Zia NA, Cullinane C, Van Zuylekom JK, Waldeck K, McInnes LE, Buncic G, Haskali MB, Roselt PD, Hicks RJ, Donnelly PS. A bivalent inhibitor of prostate specific membrane antigen radiolabeled with copper-64 with high tumor uptake and retention. Angew Chem Int Ed 2019;58(42):14991-4. https://doi.org/10.1002/anie.201908964
  41. McInnes LE, Cullinane C, Roselt PD, Jackson S, Blyth BJ, van Dam EM, Zia NA, Harris MJ, Hicks RJ, Donnelly PS. Therapeutic efficacy of a bivalent inhibitor of prostate-specific membrane antigen labeled with 67Cu. J Nucl Med 2021;62(6):829-32. https://doi.org/10.2967/jnumed.120.251579
  42. Chhabra A, Thakur ML. Theragnostic radionuclide pairs for prostate cancer management: 64Cu/67Cu, can be a budding hot duo. Biomedicines 2022;10(11):2787.
  43. Kelly JM, Ponnala S, Amor-Coarasa A, Zia NA, Nikolopoulou A, Williams Jr C, Schlyer DJ, DiMagno SG, Donnelly PS, Babich JW. Preclinical evaluation of a high-affinity sarcophagine-containing PSMA ligand for 64Cu/67Cu-based theranostics in prostate cancer. Mol Pharm 2020;17(6):1954-62. https://doi.org/10.1021/acs.molpharmaceut.0c00060
  44. Li M, Sagastume EA, Lee D, McAlister D, DeGraffenreid AJ, Olewine KR, Graves S, Copping R, Mirzadeh S, Zimmerman BE, Larsen RH, Johnson FL, Schultz MK. 203/212Pb theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer. Curr Med Chem 2020;27(41):7003-31. https://doi.org/10.2174/0929867327999200727190423
  45. Li M, Baumhover NJ, Liu D, Cagle BS, Boschetti F, Paulin G, Lee D, Dai Z, Obot ER, Marks BM, Okeil I, Sagastume EA, GabrM, Pigge FC, Johnson FL, Schultz MK. Preclinical evaluation of a lead specific chelator (PSC) conjugated to radiopeptides for 203Pb and 212Pb-based theranostics. Pharmaceutics 2023;15(2):414.
  46. Mathe D, Szigeti K, Hegedus N, Horvath I, Veres DS, Kovacs B, Szucs Z. Production and in vivo imaging of 203Pb as a surrogate isotope for in vivo 212Pb internal absorbed dose studies. Appl Radiat Isot 2016;114:1-6. https://doi.org/10.1016/j.apradiso.2016.04.015
  47. Li M, Zhang X, Quinn TP, Lee D, Liu D, Kunkel F, Zimmerman BE, McAlister D, Olewein K, Menda Y, Mirzadeh S. Automated cassette-based production of high specific activity [203/212Pb] peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer. Appl Radiat Isot 2017;127:52-60. https://doi.org/10.1016/j.apradiso.2017.05.006
  48. Dos Santos JC, Schafer M, Bauder-Wust U, Lehnert W, Leotta K, Morgenstern A, Kopka K, Haberkorn U, Mier W, Kratochwil C.Development and dosimetry of 203Pb/212Pb-labelled PSMA ligands: bringing "the lead" into PSMA-targeted alpha therapy? Eur J Nucl Med Mol Imaging 2019;46(5):1081-91. https://doi.org/10.1007/s00259-018-4220-z
  49. Stenberg VY, Juzeniene A, Chen Q, Yang X, Bruland OS, Larsen RH. Preparation of the alpha emitting prostate specific membrane antigen targeted radioligand [212Pb]PbNG001 for prostate cancer. J Labelled Comp Radiopharm 2020;63(3):129-43. https://doi.org/10.1002/jlcr.3825