Radiolabeled peptides inhibitors of PSMA for the study of prostate carcinoma
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Keywords:
peptides, antigens, prostate, neoplasms, single photon emission computed tomography, positron computed tomography, radiopharmaceuticals
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Abstract
Prostate cancer, with a high incidence and as the second cause of death among the male population, constitutes a serious health problem that worsens over the years. The early diagnosis and the correct staging of this disease are important for the adequate management of the patient. In this sense, Nuclear Medicine molecular imaging is very useful, so the development of new peptidomimetic molecules with affinity for membrane receptors overexpressed in prostate cancer, such as prostate specific antigen (PSMA), has allowed making a qualitative step forward for the early detection and monitoring of prostate carcinoma. The present work is aimed at providing an overview of the status of PSMA inhibitor peptides, derived from the sequence -Lys-Urea-Glu-, as radiopharmaceuticals for the study of prostate neoplasms, which are currently in different stages of development, showing, in general, a high specificity, an adequate uptake into the tumor tissue and a satisfactory pharmacokinetics, to be used in the study of prostate cancer, both by positron emission tomography (PET), and by single photon emission computed tomography (SPECT).
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How to Cite
Perera Pintado, A., Prats Capote, A., & Cruz Arencibia, J. (1). Radiolabeled peptides inhibitors of PSMA for the study of prostate carcinoma. Nucleus, (72), 40-47. Retrieved from http://nucleus.cubaenergia.cu/index.php/nucleus/article/view/773
Section
Ciencias Nucleares
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References
[1]. TEOH JYC, HIRAI HW, HO JMW, et. al. Global incidence of prostate cancer in developing and developed countries with changing age structures. PLoS ONE. 2019; 14(10): e0221775.
[2]. Cuba. Ministerio de Salud Pública (MINSAP). Dirección de Registros Médicos y Estadísticas de Salud. Anuario estadístico de salud. MINSAP, 2020.
[3]. PILLAI MRA, NANABALA R, JOY A, et. al. Radiolabeled enzyme inhibitors and binding agents targeting PSMA: effective theranostic tools for imaging and therapy of prostate cancer. Nucl Med Biol. 2016; 43(11): 692-720. doi: 10.1016/j.nucmedbio.2016.08.006.
[4]. RAWLA P. Epidemiology of Prostate Cancer. World J Oncol 2019; 10(2): 63-89.
[5]. HABERKORN U, EDER M, KOPKA K, et. al. New strategies in prostate cancer: prostate-specific membrane antigen (PSMA) ligands for diagnosis and therapy. Clin Cancer Res. 2016; 22: 9-15.
[6]. 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: 4504-4517.
[7]. LIU J, CHEN Z, WANG T, LIU L, et. al. Influence of four radiotracers in PET/CT on diagnostic accuracy for prostate cancer: a bivariate random-effects meta-analysis. Cell Physiol Biochem. 2016; 39: 467-480.
[8]. BALLAS LK, ABREU ALC, QUINN DI. What medical, urologic, radiation oncologists want from molecular imaging of prostate cancer. J Nucl Med. 2016; 57: 6S-12S.
[9]. LENZO NP, MEYRICK D, HARVEY TURNER J. Review of Gallium-68 PSMA PET/CT Imaging in the management of prostate cancer. Diagnostics. 2018; 8: 16. doi: 10.3390/diagnostics8010016.
[10]. SU H, ZHU Y, LING G, HU S, et. al. Evaluation of 99mTc-labeled PSMA-SPECT/CT imaging in prostate cancer patients who have undergone biochemical relapse. Asian J Androl. 2017; 19: 267-271.
[11]. JADVAR H. PET glucose metabolism and cellular proliferation in prostate cancer. J Nucl Med. 2016; 57: 25S-29S.
[12]. MAPELLI P, INCERTI E, CECI F, et. al. 11C- or 18F-Choline PET/CT for imaging evaluation of biochemical recurrence of prostate cancer. J Nucl Med. 2016; 57: 43S-48S.
[13]. CECI F, CASTELLUCCI P, MAPELLI P, et. al. Evaluation of prostate cancer with 11C-choline PET/CT for treatment planning, response assessment, and prognosis. J Nucl Med. 2016; 57: 49S-54S.
[14]. Kopka K, Benesova 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: 17S-26S.
[15]. RAHBAR K, AFSHAR-OROMIEH A, JADVAR H, AHMADZADEHFAR H. PSMA theranostics: current status and future directions. Mol Imaging. 2018; 17: 1-9. doi: 10.1177/1536012118776068.
[16]. GOURNI E, HENRIKSEN G. Metal-based PSMA radioligands. Molecules. 2017; 22: 523. doi:10.3390/molecules22040523
[17]. EVANS JC, MALHOTRA M, CRYAN JF, O’DRISCOLL CM. The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease. British J Pharm. 2016; 173: 3041-3079.
[18]. BOSCHI A, UCCELLI L, MARTINI P. A picture of modern tc-99m radiopharmaceuticals: production, chemistry, and applications in molecular imaging. Appl Sci. 2019; 9, 2526. DOI: 10.3390/app9122526.
[19]. PANDIT-TASKAR N, VEACH DR, FOX JJ, et. al. Evaluation of castration-resistant prostate cancer with androgen receptor-axis imaging. J Nucl Med. 2016; 57: 73S-78S.
[20]. WU M, SHU J. Multimodal molecular imaging: current status and future directions. Contrast Media Mol Imaging. 2018: 1382183. doi: 10.1155/2018/1382183
[21]. OLIVA GONZÁLEZ JP, MARTÍNEZ RAMÍREZ A, BAUM RP. Aplicaciones del PET/CT en oncología. Nucleus. 2017; (62): 10-12.
[22]. International Atomic Energy Agency (IAEA). Cyclotron produced radionuclides: physical characteristics and production methods. Technical Reports Series No. 468. Vienna: IAEA , 2009.
[23]. VIRGOLINI I, DECRISTOFORO C, HAUG A, et. al. Current status of theranostics in prostate cancer. Eur J Nucl Med Mol Imaging. 2018; 45: 471-495.
[24]. CZARNIECKI M, MENA E, LINDENBERG L, et. al. Keeping up with the prostate-specific membrane antigens (PSMAs): an introduction to a new class of positron emission tomography (PET) imaging agents. Transl Androl Urol. 2018; 7(5):831-843.
[25]. KLEIN NULENT TJW, VAN ES RJJ, Krijger GC, et. al. Prostate-specific membrane antigen PET imaging and immunohistochemistry in adenoid cystic carcinoma - a preliminary analysis. Eur J Nucl Med Mol Imaging. 2017; 44: 1614-1621.
[26]. GOURNI E, DEL POZZO L, BARTHOLOMA M, et. al. Radiochemistry and preclinical PET imaging of 68Ga-desferrioxamine radiotracers targeting prostate-specific membrane antigen. Mol Imaging. 2017; 16: 1-11. doi: 10.1177/1536012117737010
[27]. FENDLER WP, EIBER M, BEHESHTI M, et. al 68Ga-PSMA PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017. dOI 10.1007/s00259-017-3670-z
[28]. YOUNG JD, ABBATE V, IMBERTI C, et. al. 68Ga-THP-PSMA: a PET imaging agent for prostate cancer offering rapid, room temperature, one-step kit-based radiolabeling. J Nucl Med. 2017; 58: 1270-1277.
[29]. PASTORINO S, RIONDATO M, Uccelli L, et. al. Toward the discovery and development of psma targeted inhibitors for nuclear medicine applications. Curr Radiopharm. 2020; 13: 63-79.
[30]. GIESEL FL, KNORR K, SPOHN F, et. al. Detection efficacy of 18F-PSMA-1007 PET/CT in 251 patients with biochemical recurrence of prostate cancer after radical prostatectomy. J Nucl Med. 2019; 60: 362-368.
[31]. CLEEREN F, LECINANJ, BILLAUD EMF, et. al New chelators for low temperature Al18F-labeling of biomolecules. Bioconjugate Chem. 2016; 27; 790-798.
[32]. GIGLIO J, ZENI M, SAVIO E, ENGLER H. Synthesis of an Al18F radiofluorinated GLUUREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform. EJNMMI Radiopharm Chem. 2018; 3: 4. doi: 10.1186/s41181-018-0039-y.
[33]. HASSAN H, RAZAK HRA, SAAD FFA, KUMAR V. 18F[AlF]-radiolabelled Peptides on the Automated Synthesis Platform: Translating the Laboratory Bench Work to Bedside. Malays J Med Sci. 2019; 26: 122-126.
34 [34]. CUI C, HANYU M, HATORI A, et. al. Synthesis and evaluation of [64Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer. Am J Nucl Med Mol Imaging. 2017; 7:40-52.
[35]. MÜLLER C, DOMNANICH KA, UMBRICHT CA, VAN DER MEULEN NP. Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application. Br J Radiol. 2018; 91: 20180074.
[36]. Pedersen KS, Baun C, Nielsen KM, Thisgaard H, et. al. Design, Synthesis, Computational, and Preclinical Evaluation of natTi/45Ti-Labeled Urea-Based Glutamate PSMA Ligand. Molecules 2020; 25: 1104. DOI:10.3390/molecules25051104
[37]. PERERA PINTADO A, TORRES AROCHE LA, VERGARA GIL A, et. al. SPECT/CT: principales aplicaciones en la medicina nuclear. Nucleus. 2017; (62): 2-9.
[38]. BARRETT JA, COLEMAN E, GOLDSMITH SJ, et. al. First-in-Man Evaluation of 2 High-Affinity PSMA-Avid Small Molecules for Imaging Prostate Cancer. J Nucl Med. 2013; 54: 380-387.
[39]. BANERJEE RS, PULLAMBHATLA M, FOSS CA, et. al. Effect of chelators on the pharmacokinetics of (99m)Tc-labeled imaging agents for the prostate-specific membrane antigen (PSMA). J Med Chem. 2013; 56: 6108-6121.
[40]. FERRO FLORES G, LUNA GUTIÉRREZ M, OCAMPO GARCÍA B, et. al. Clinical translation of a PSMA inhibitor for 99mTc-based SPECT. Nucl Med Biol. 2017; 48: 36-44.
[41]. XU X, ZHANG J, HU S, et. al. 99mTc-labeling and evaluation of a HYNIC modified small-molecular inhibitor of prostate-specific membrane antigen. Nucl Med Biol. 2017; 48: 69-75.
[42]. 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: 235-242.
[43]. HENDRIKX JJMA. Automated synthesis and quality control of [99mTc]Tc-PSMA for radioguided surgery (in a [68Ga]Ga-PSMA workflow). EJNMMI Radiopharm Chem. 2020; 5: 10. doi: 10.1186/s41181-020-00095-9
[44]. WERNER P, NEUMANN C, EIBER M, et. al. [99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center. EJNMMI Res. 2020; 10: 45. doi: 10.1186/s13550-020-00635-z.
[45]. VATS K, AGRAWAL K, SHARMA R, et. al. Preparation and clinical translation of 99mTc-PSMA-11 for SPECT imaging of prostate cancer. Med Chem Commun. 2019; 10: 2111-2117.
[2]. Cuba. Ministerio de Salud Pública (MINSAP). Dirección de Registros Médicos y Estadísticas de Salud. Anuario estadístico de salud. MINSAP, 2020.
[3]. PILLAI MRA, NANABALA R, JOY A, et. al. Radiolabeled enzyme inhibitors and binding agents targeting PSMA: effective theranostic tools for imaging and therapy of prostate cancer. Nucl Med Biol. 2016; 43(11): 692-720. doi: 10.1016/j.nucmedbio.2016.08.006.
[4]. RAWLA P. Epidemiology of Prostate Cancer. World J Oncol 2019; 10(2): 63-89.
[5]. HABERKORN U, EDER M, KOPKA K, et. al. New strategies in prostate cancer: prostate-specific membrane antigen (PSMA) ligands for diagnosis and therapy. Clin Cancer Res. 2016; 22: 9-15.
[6]. 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: 4504-4517.
[7]. LIU J, CHEN Z, WANG T, LIU L, et. al. Influence of four radiotracers in PET/CT on diagnostic accuracy for prostate cancer: a bivariate random-effects meta-analysis. Cell Physiol Biochem. 2016; 39: 467-480.
[8]. BALLAS LK, ABREU ALC, QUINN DI. What medical, urologic, radiation oncologists want from molecular imaging of prostate cancer. J Nucl Med. 2016; 57: 6S-12S.
[9]. LENZO NP, MEYRICK D, HARVEY TURNER J. Review of Gallium-68 PSMA PET/CT Imaging in the management of prostate cancer. Diagnostics. 2018; 8: 16. doi: 10.3390/diagnostics8010016.
[10]. SU H, ZHU Y, LING G, HU S, et. al. Evaluation of 99mTc-labeled PSMA-SPECT/CT imaging in prostate cancer patients who have undergone biochemical relapse. Asian J Androl. 2017; 19: 267-271.
[11]. JADVAR H. PET glucose metabolism and cellular proliferation in prostate cancer. J Nucl Med. 2016; 57: 25S-29S.
[12]. MAPELLI P, INCERTI E, CECI F, et. al. 11C- or 18F-Choline PET/CT for imaging evaluation of biochemical recurrence of prostate cancer. J Nucl Med. 2016; 57: 43S-48S.
[13]. CECI F, CASTELLUCCI P, MAPELLI P, et. al. Evaluation of prostate cancer with 11C-choline PET/CT for treatment planning, response assessment, and prognosis. J Nucl Med. 2016; 57: 49S-54S.
[14]. Kopka K, Benesova 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: 17S-26S.
[15]. RAHBAR K, AFSHAR-OROMIEH A, JADVAR H, AHMADZADEHFAR H. PSMA theranostics: current status and future directions. Mol Imaging. 2018; 17: 1-9. doi: 10.1177/1536012118776068.
[16]. GOURNI E, HENRIKSEN G. Metal-based PSMA radioligands. Molecules. 2017; 22: 523. doi:10.3390/molecules22040523
[17]. EVANS JC, MALHOTRA M, CRYAN JF, O’DRISCOLL CM. The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease. British J Pharm. 2016; 173: 3041-3079.
[18]. BOSCHI A, UCCELLI L, MARTINI P. A picture of modern tc-99m radiopharmaceuticals: production, chemistry, and applications in molecular imaging. Appl Sci. 2019; 9, 2526. DOI: 10.3390/app9122526.
[19]. PANDIT-TASKAR N, VEACH DR, FOX JJ, et. al. Evaluation of castration-resistant prostate cancer with androgen receptor-axis imaging. J Nucl Med. 2016; 57: 73S-78S.
[20]. WU M, SHU J. Multimodal molecular imaging: current status and future directions. Contrast Media Mol Imaging. 2018: 1382183. doi: 10.1155/2018/1382183
[21]. OLIVA GONZÁLEZ JP, MARTÍNEZ RAMÍREZ A, BAUM RP. Aplicaciones del PET/CT en oncología. Nucleus. 2017; (62): 10-12.
[22]. International Atomic Energy Agency (IAEA). Cyclotron produced radionuclides: physical characteristics and production methods. Technical Reports Series No. 468. Vienna: IAEA , 2009.
[23]. VIRGOLINI I, DECRISTOFORO C, HAUG A, et. al. Current status of theranostics in prostate cancer. Eur J Nucl Med Mol Imaging. 2018; 45: 471-495.
[24]. CZARNIECKI M, MENA E, LINDENBERG L, et. al. Keeping up with the prostate-specific membrane antigens (PSMAs): an introduction to a new class of positron emission tomography (PET) imaging agents. Transl Androl Urol. 2018; 7(5):831-843.
[25]. KLEIN NULENT TJW, VAN ES RJJ, Krijger GC, et. al. Prostate-specific membrane antigen PET imaging and immunohistochemistry in adenoid cystic carcinoma - a preliminary analysis. Eur J Nucl Med Mol Imaging. 2017; 44: 1614-1621.
[26]. GOURNI E, DEL POZZO L, BARTHOLOMA M, et. al. Radiochemistry and preclinical PET imaging of 68Ga-desferrioxamine radiotracers targeting prostate-specific membrane antigen. Mol Imaging. 2017; 16: 1-11. doi: 10.1177/1536012117737010
[27]. FENDLER WP, EIBER M, BEHESHTI M, et. al 68Ga-PSMA PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017. dOI 10.1007/s00259-017-3670-z
[28]. YOUNG JD, ABBATE V, IMBERTI C, et. al. 68Ga-THP-PSMA: a PET imaging agent for prostate cancer offering rapid, room temperature, one-step kit-based radiolabeling. J Nucl Med. 2017; 58: 1270-1277.
[29]. PASTORINO S, RIONDATO M, Uccelli L, et. al. Toward the discovery and development of psma targeted inhibitors for nuclear medicine applications. Curr Radiopharm. 2020; 13: 63-79.
[30]. GIESEL FL, KNORR K, SPOHN F, et. al. Detection efficacy of 18F-PSMA-1007 PET/CT in 251 patients with biochemical recurrence of prostate cancer after radical prostatectomy. J Nucl Med. 2019; 60: 362-368.
[31]. CLEEREN F, LECINANJ, BILLAUD EMF, et. al New chelators for low temperature Al18F-labeling of biomolecules. Bioconjugate Chem. 2016; 27; 790-798.
[32]. GIGLIO J, ZENI M, SAVIO E, ENGLER H. Synthesis of an Al18F radiofluorinated GLUUREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform. EJNMMI Radiopharm Chem. 2018; 3: 4. doi: 10.1186/s41181-018-0039-y.
[33]. HASSAN H, RAZAK HRA, SAAD FFA, KUMAR V. 18F[AlF]-radiolabelled Peptides on the Automated Synthesis Platform: Translating the Laboratory Bench Work to Bedside. Malays J Med Sci. 2019; 26: 122-126.
34 [34]. CUI C, HANYU M, HATORI A, et. al. Synthesis and evaluation of [64Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer. Am J Nucl Med Mol Imaging. 2017; 7:40-52.
[35]. MÜLLER C, DOMNANICH KA, UMBRICHT CA, VAN DER MEULEN NP. Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application. Br J Radiol. 2018; 91: 20180074.
[36]. Pedersen KS, Baun C, Nielsen KM, Thisgaard H, et. al. Design, Synthesis, Computational, and Preclinical Evaluation of natTi/45Ti-Labeled Urea-Based Glutamate PSMA Ligand. Molecules 2020; 25: 1104. DOI:10.3390/molecules25051104
[37]. PERERA PINTADO A, TORRES AROCHE LA, VERGARA GIL A, et. al. SPECT/CT: principales aplicaciones en la medicina nuclear. Nucleus. 2017; (62): 2-9.
[38]. BARRETT JA, COLEMAN E, GOLDSMITH SJ, et. al. First-in-Man Evaluation of 2 High-Affinity PSMA-Avid Small Molecules for Imaging Prostate Cancer. J Nucl Med. 2013; 54: 380-387.
[39]. BANERJEE RS, PULLAMBHATLA M, FOSS CA, et. al. Effect of chelators on the pharmacokinetics of (99m)Tc-labeled imaging agents for the prostate-specific membrane antigen (PSMA). J Med Chem. 2013; 56: 6108-6121.
[40]. FERRO FLORES G, LUNA GUTIÉRREZ M, OCAMPO GARCÍA B, et. al. Clinical translation of a PSMA inhibitor for 99mTc-based SPECT. Nucl Med Biol. 2017; 48: 36-44.
[41]. XU X, ZHANG J, HU S, et. al. 99mTc-labeling and evaluation of a HYNIC modified small-molecular inhibitor of prostate-specific membrane antigen. Nucl Med Biol. 2017; 48: 69-75.
[42]. 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: 235-242.
[43]. HENDRIKX JJMA. Automated synthesis and quality control of [99mTc]Tc-PSMA for radioguided surgery (in a [68Ga]Ga-PSMA workflow). EJNMMI Radiopharm Chem. 2020; 5: 10. doi: 10.1186/s41181-020-00095-9
[44]. WERNER P, NEUMANN C, EIBER M, et. al. [99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center. EJNMMI Res. 2020; 10: 45. doi: 10.1186/s13550-020-00635-z.
[45]. VATS K, AGRAWAL K, SHARMA R, et. al. Preparation and clinical translation of 99mTc-PSMA-11 for SPECT imaging of prostate cancer. Med Chem Commun. 2019; 10: 2111-2117.