Radiopharmaceuticals for Bone Metastases

Chapter

Abstract

Bone-seeking radiopharmaceuticals play a significant role in the treatment of metastatic pain as an alternative, or in addition, to classic palliative treatment.

Until a few years ago, radionuclides for the management of prostate cancer consisted of several beta-emitting agents, such as strontium (89Sr), phosphorus (32P) and samarium (153Sm) as well as rhenium (186Re and 188Re), which only exhibit a palliative effect in patients with extensive skeletal disease.

Radium (223Ra) dichloride represents a new generation of radiopharmaceuticals, being the first targeted alpha-emitting agent approved, which improves overall survival, postpones skeletal-related events (SREs) and controls bone pain.

Conjugates of bisphosphonates (BP) with macrocyclic chelators open new possibilities in bone-targeted radionuclide imaging and therapy, when labelled with positron and beta-emitting radiometals. [68Ga/177Lu]DOTAZOL appears to be the best leading compound showing fast blood clearance, low uptake in soft tissue and high accumulation in the skeleton.

Prostate-specific membrane antigen (PSMA) is an attractive target for diagnosis and therapy of prostate cancer. 177Lu-PSMA-617 is a new treatment option, which is not solely directed to bone metastases, but also demonstrates “antitumour” activity with limited and well-tolerated side effects.

References

  1. 1.
    Liepe K, Shinto A. From palliative therapy to prolongation of survival: 223RaCl2 in the treatment of bone metastases. Ther Adv Med Oncol. 2016;8(4):294–304.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Maffioli L, Florimonte L, Costa DC, et al. New radiopharmaceutical agents for the treatment of castration-resistant prostate cancer. Q J Nucl Med Mol Imaging. 2015;59:420–38.PubMedGoogle Scholar
  3. 3.
    Guerra Liberal FDC, Tavares AAS, Tavares JMRS. Palliative treatment of metastatic bone pain with radiopharmaceuticals: a perspective beyond Strontium-89 and Samarium-153. Appl Rad Isotope. 2016;110:87–99.CrossRefGoogle Scholar
  4. 4.
    Bienz M, Saad F. Management of bone metastases in prostate cancer: a review. Curr Opin Support Palliat Care. 2015;9:261–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Blacksburg SR, Witten MR, Haas JA. Integrating bone targeting radiopharmaceuticals into the management of patients with castrate-resistant prostate cancer with symptomatic bone metastases. Curr Treat Options in Oncol. 2015;16:11.CrossRefGoogle Scholar
  6. 6.
    Liepe K, Runge R, Kotzerke J. The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain. J Cancer Res Clin Oncol. 2005;131:60–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Bellmunt J. Tackling the bone with alpha emitters in metastatic castration-resistant prostate cancer patients. Eur Urol. 2013;63:198–200.CrossRefPubMedGoogle Scholar
  8. 8.
    Goyal J, Antonarakis ES. Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases. Cancer Lett. 2012;323:135–46.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Das T, Banerjee S. Radiopharmaceuticals for metastatic bone pain palliation: available options in the clinical domain and their comparisons. Clin Exp Metastasis. 2016;34(1):1–10.CrossRefPubMedGoogle Scholar
  10. 10.
    Srivastava SC, Mausner LF. Therapeutic radionuclides: production, physical characteristics, and applications. In: Baum RP, editor. Therapeutic nuclear medicine. Heidelberg: Springer; 2013.Google Scholar
  11. 11.
    Lewis B, Sartor O. Radiation-based approaches for therapy and palliation of advanced prostate cancer. Curr Opin Urol. 2012;22:183–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Knapp FF, Dash A. Radiopharmaceuticals for therapy. India: Springer; 2016.Google Scholar
  13. 13.
    Sartor O, Hoskin P, Bruland ØS. Targeted radio-nuclide therapy of skeletal metastases. Cancer Treat Rev. 2013;39:18–26.CrossRefPubMedGoogle Scholar
  14. 14.
    Das T, Pillai MRA. Options to meet the future global demand of radionuclides for radionuclide therapy. Nucl Med Biol. 2013;40:23–32.CrossRefPubMedGoogle Scholar
  15. 15.
    Riondato M, Eckelman WC. In: Ciarmiello A, Mansi L, editors. Radiopharmaceuticals. PET-CT and PET-MRI in neurology. SWOT analysis applied to hybrid imaging, vol. 4. Part I ed. Switzerland: Springer; 2016. p. 31–58.Google Scholar
  16. 16.
    Silberstein EB. Teletherapy and radiopharmaceutical therapy of painful bone metastases. Semin Nucl Med. 2005;35:152–8.CrossRefPubMedGoogle Scholar
  17. 17.
    van Dodewaard-de JM, Oprea-Lager DE, Hooft L, et al. Radiopharmaceuticals for palliation of bone pain in patients with castration- resistant prostate cancer metastatic to bone: a systematic review. Eur Urol. 2016;70:416–26.CrossRefGoogle Scholar
  18. 18.
    Rubini G, Nicoletti A, Rubini D, Niccoli A. Radiometabolic treatment of bone-metastasizing cancer: from 186Renium to 223Radium. Cancer Biother Radiopharm. 2013;29(1):1–11.CrossRefPubMedGoogle Scholar
  19. 19.
    Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol. 2005;6(6):392–400.CrossRefPubMedGoogle Scholar
  20. 20.
    Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med. 2005;46:38S–47S.PubMedGoogle Scholar
  21. 21.
    Bergmann R, Meckel M, Kubíček V, et al. 177Lu-labelled macrocyclic bisphosphonates for targeting bone metastasis in cancer treatment. EJNMMI Res. 2016;6:5.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Meckel M, Bergmann R, Miederer M, Roesch F. Bone targeting compounds for radiotherapy and imaging: *me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid. EJNMMI Radiopharmacy Chem. 2016;1:14.CrossRefGoogle Scholar
  23. 23.
    Rachner TD, Jakob F, Hofbauer LC. Cancer-targeted therapies and radiopharmaceuticals. Bonekey Reports. 2015;4:707.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hofbauer LC, Rachner TD, Coleman RE, Jakob F. Endocrine aspects of bone metastases. Lancet Diabetes Endocrinol. 2014;2(6):500–12.CrossRefPubMedGoogle Scholar
  25. 25.
    Mantyh PW. Bone cancer pain: from mechanism to therapy. Curr Opin Support Palliat Care. 2014;8(2):83–90.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Abi-Ghanem AS, McGrath MA, Jacene HA. Radionuclide therapy for osseous metastases in prostate. Cancer Semin Nucl Med. 2015;45:66–80.CrossRefPubMedGoogle Scholar
  27. 27.
    Baidoo KE, Yong K, Brechbiel M. Molecular pathways: targeted alpha-particle radiation therapy. Clin Cancer Res. 2013;19(3):530–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Florimonte L, Dellavedova L, Maffioli LS. Radium-223 dichloride in clinical practice: a review. Eur J Nucl Med Mol Imaging. 2016;43(10):1896–909.CrossRefPubMedGoogle Scholar
  29. 29.
    Sartor O. Radiopharmaceuticals: a path forward. Eur Urol. 2016;70:427–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Emmett L, Kathy Willowson K, et al. Lutetium-177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 2017;64(1):52–60.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Afshar-Oromieh A, Hetzheim H, Kratochwil C, et al. The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med. 2015;56:1697–705.CrossRefPubMedGoogle Scholar
  32. 32.
    Clinical guideline [CG175]. 2014. http://www.nice.org.uk/guidance/cg175
  33. 33.
    Italian Medicines Agency, European Public Assessment Report (EPAR) Strontium [89Sr] dichloride (last updated 10 June 2016. http://www.aifa.gov.it/en.
  34. 34.
    Delacroix D, Guerre JP, Leblanc P, Hickman C. Radionuclide and radiation protection data handbook. Radiat Prot Dosim. 2002;98:1.CrossRefGoogle Scholar
  35. 35.
    Lam MGEH, de Klerk JMH, van Rijk PP, Zonnenberg BA. Bone seeking radiopharmaceuticals for palliation of pain in cancer patients with osseous metastases. Anti Cancer Agents Med Chem. 2007;7:381–97.CrossRefGoogle Scholar
  36. 36.
    Ogawa K, Washiyama K. Bone target radiotracers for palliative therapy of bone metastases. Curr Med Chem. 2012;19:3290–300.CrossRefPubMedGoogle Scholar
  37. 37.
    Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med. 2004;45:1358–65.PubMedGoogle Scholar
  38. 38.
    Paes FM, Ernani V, Hosein P, Serafi ni AN. Radiopharmaceuticals: when and how to use them to treat metastatic bone pain. J Support Oncol. 2011;9:197–205.CrossRefPubMedGoogle Scholar
  39. 39.
    Morris MJ, Scher HI. Clinical approaches to osseous metastases in prostate cancer. Oncologist. 2003;8(2):161–73.CrossRefPubMedGoogle Scholar
  40. 40.
    Gravalos C, Rodriguez C, Sabino A, et al. SEOM clinical guideline for bone metastases from solid tumours (2016). Clin Transl Oncol. 2016;18:1243–53.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Nilsson S. Radionuclide therapies in prostate cancer: integrating radium-223 in the treatment of patients with metastatic castration-resistant prostate. Cancer Curr Oncol Rep. 2016;18:14.CrossRefPubMedGoogle Scholar
  42. 42.
    Tucci M, Scagliotti GV, Vignani F. Metastatic castration-resistant prostate cancer: time for innovation. Future Oncol. 2015;11(1):91–106.CrossRefPubMedGoogle Scholar
  43. 43.
    Harrison MR, Wong TZ, Armstrong AJ, George DJ. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease. Cancer Manag Res. 2013;5:1–14.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    El-Amm J, Aragon-Ching JB. Radium-223 for the treatment of castration-resistant prostate cancer. Oncol Targets Therap. 2015;8:1103–9.CrossRefGoogle Scholar
  45. 45.
    Pandit-Taskar N, Larson SM, Carrasquillo JA. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, part 1: a therapy with 223Ra-dichloride. J Nucl Med. 2014;55:268–74.CrossRefPubMedGoogle Scholar
  46. 46.
    Jadvar H, Quinn DI. Targeted alpha-particle therapy of bone metastases in prostate cancer. Clin Nucl Med. 2013;38:966–71.PubMedGoogle Scholar
  47. 47.
    European Medicines Agency (EMA) European Public Assessment Report (EPAR) radium [223Ra] dichloride (last updated 2016). http://www.ema.europa.eu/ema/.
  48. 48.
    Lien LME, Tvedt B, Heinrich D. Treatment of castration-resistant prostate cancer and bone metastases with radium-223 dichloride. Int J Urol Nurs. 2015;9:3–13.CrossRefPubMedGoogle Scholar
  49. 49.
    Buroni FE, Persico MG, Pasi F, et al. Review radium-223: insight and perspectives in bone-metastatic castration-resistant prostate cancer. Anticancer Res. 2016;36:5719–30.CrossRefPubMedGoogle Scholar
  50. 50.
    Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.CrossRefPubMedGoogle Scholar
  51. 51.
    Ryan CJ, Saylor PJ, Everly JJ, Sartor O. Bone-targeting radiopharmaceuticals for the treatment of bone-metastatic castration-resistant prostate cancer: exploring the implications of new data. Oncologist. 2014;19(10):1012–8.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Nilsson S. Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety. Expert Opin Drug Saf. 2015;14(7):1127–36.CrossRefPubMedGoogle Scholar
  53. 53.
    Sartor O, Coleman R, Nilsson S, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014;15:738–46.CrossRefPubMedGoogle Scholar
  54. 54.
    Shore ND. Radium-223 dichloride for metastatic castration-resistant prostate cancer: the urologist’s perspective. Urology. 2015;85(4):717–24.CrossRefPubMedGoogle Scholar
  55. 55.
    Cheetham PJ, Petrylak DP. Alpha particles as radiopharmaceuticals in the treatment of bone metastases: mechanism of action of radium-223 chloride (Alpharadin) and radiation. Oncology (Williston Park). 2012;26(4):330–41.Google Scholar
  56. 56.
    Coleman R. Treatment of metastatic bone disease and the emerging role of radium-223. Semin Nucl Med. 2016;46:99–104.CrossRefPubMedGoogle Scholar
  57. 57.
    Shirley M, McCormack PL. Radium-223 dichloride: a review of its use in patients with castration resistant prostate cancer with symptomatic bone metastases. Drugs. 2014;74:579–86.CrossRefPubMedGoogle Scholar
  58. 58.
    Wieder HA, Lassmann M, Allen-Auerbach MS, et al. Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters. World J Radiol. 2014;6(7):480–5.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Bombardieri E, Evangelista L, Ceresoli GL, Boccardo F. Nuclear medicine and the revolution in the modern management of castration-resistant prostate cancer patients: from 223Ra-dichloride to new horizons for therapeutic response assessment. Eur J Nucl Med Mol Imaging. 2016;43:5–7.CrossRefPubMedGoogle Scholar
  60. 60.
    El-Amm J, Freeman A, Patel N, Aragon-Ching JB. Bone-targeted therapies in metastatic castration-resistant prostate cancer: evolving paradigms. Prostate Cancer. 2013;2013:210686.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Iagaru AH, Mittra E, Colletti PM, Jadvar H. Bone-targeted imaging and radionuclide therapy in prostate cancer. J Nucl Med. 2016;57:19S–24S.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Baldari S, Boni G, Bortolus R, et al. Management of metastatic castration-resistant prostate cancer: a focus on radium-223 opinions and suggestions from an expert multidisciplinary panel. Crit Rev. Oncol Hematol. 2017;113:43–51.CrossRefPubMedGoogle Scholar
  63. 63.
    European Pharmacopoeia 5.0 “Sodium phosphate (32P) injection” (Ph Eur monograph 0284) (01/2005).Google Scholar
  64. 64.
    USP monographs: Sodium phosphate P 32 solution. 2005. USP29-NF2:1727.Google Scholar
  65. 65.
    Vimalnath KV, Shetty P, Chakraborty S, et al. Practicality of production of 32P by direct neutron activation for its utilization in bone pain palliation as Na3[32P]PO4. Cancer Biother Radiopharm. 2013;28:423–8.CrossRefPubMedGoogle Scholar
  66. 66.
    Sartor O, Reid RH, Hoskin PJ, et al. Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone refractory prostate cancer. Urology. 2004;63:940–5.CrossRefPubMedGoogle Scholar
  67. 67.
    European Medicines Agency (EMA) European Public Assessment Report (EPAR) Samarium [153Sm] lexidronam (last updated 2015). http://www.ema.europa.eu/ema.
  68. 68.
    Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. Semin Nucl Med. 2010;40:89–104.CrossRefPubMedGoogle Scholar
  69. 69.
    Anderson P. Samarium for osteoblastic bone metastases and osteosarcoma. Expert Opin Pharmacother. 2006;7:1475–86.CrossRefPubMedGoogle Scholar
  70. 70.
    Pillai MRA, Dash A, Knapp FF Jr. Rhenium-188: availability from the 188W/188Re generator and status of current applications. Curr Radiopharm. 2012;5:228–43.CrossRefPubMedGoogle Scholar
  71. 71.
    Bodei L, Lam M, Chiesa C, et al. EANM procedure guideline for treatment of refractory metastatic bone pain. Eur J Nucl Med Mol Imaging EANM. 2008;35(10):1934–40.CrossRefGoogle Scholar
  72. 72.
    Minutoli F, Herberg A, Spadaro P. [186Re]-HEDP in the palliation of painful bone metastases from cancers other than prostate and breast. Q J Nucl Med Mol Imaging. 2006;50:355–62.PubMedGoogle Scholar
  73. 73.
    Knapp FF Jr, Beets AL, Pinkert J, et al. Rhenium radioisotopes for therapeutic radiopharmaceutical development. Inter seminar on therapeutic applications of radiopharmaceuticals (IAEA-SR-209), Hyderabad, India. 1999.Google Scholar
  74. 74.
    Boschi A, Uccelli L, Pasquali M, et al. 188 W/188Re generator system and its therapeutic applications. J Chemom. 2014;2014:529406.Google Scholar
  75. 75.
    Argyrou M, Valassi A, Andreou M, Lyra M. Rhenium-188 production in hospitals, by W-188/re-188 generator, for easy use in radionuclide therapy. Int J Mol Imaging. 2013;2013:290750.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Liepe K, Kropp J, RungeR KJ. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br J Cancer. 2003;89:625–9.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Yousefnia H, Zolghadri S, Sadeghi HR. Preparation and biological assessment of 177Lu-BPAMD as a high potential agent for bone pain palliation therapy: comparison with 177Lu-EDTMP. J Radioanal Nucl Chem. 2015;307:1243–51.CrossRefGoogle Scholar
  78. 78.
    Meckel M. Macrocyclic bisphosphonates for PET-diagnosis and endoradiotherapy of bone metastases [Dissertation]; 2014.Google Scholar
  79. 79.
    Banerjee S, Pillai MRA, Knapp FF Jr. Lutetium-177 therapeutic radiopharmaceuticals-linking chemistry, radiochemistry and practical applications. Chem Rev. 2015;115:2934–74.CrossRefPubMedGoogle Scholar
  80. 80.
    Dash A, Pillai MRA, Knapp FF. Production of 177Lu for targeted radionuclide therapy: available options. Nucl Med Mol Imaging. 2015;49:85–107.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    European Medicines Agency (EMA) European Public Assessment Report (EPAR) Lutetium (177Lu) chloride (last updated 2017). http://www.ema.europa.eu/ema.
  82. 82.
    Meckel M, Kubíček V, Hermann P, et al. A DOTA based bisphosphonate with an albumin binding moiety for delayed body clearance for bone targeting. Nucl Med Biol. 2016;43:670–8.CrossRefPubMedGoogle Scholar
  83. 83.
    Rasheed R, Lodhi NA, Khalid M, et al. Radio-synthesis, and in-vivo skeletal localization of 177Lu- zoledronic acid as novel bone seeking therapeutic radiopharmaceutical. J Anesth Clin Res. 2015;6:516.CrossRefGoogle Scholar
  84. 84.
    European Medicines Agency (EMA) European Public Assessment Report (EPAR) Zoledronic acid (last updated 2016). http://www.ema.europa.eu/ema.
  85. 85.
    Kiess AP, Banerjee SR, Mease RC, et al. Prostate-specific membrane antigen as a target for cancer imaging and therapy. Q J Nucl Med Mol Imaging. 2015;59:241–68.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Baum RP, Kulkarni HR, Schuchardt C, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57:1006–13.CrossRefPubMedGoogle Scholar
  87. 87.
    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;43:692–720.CrossRefPubMedGoogle Scholar
  88. 88.
    Wüstemann T, Bauder-Wüst U, Schäfer M, et al. Design of internalizing PSMA-specific Glu-ureido-based radiotherapeuticals. Theranostics. 2016;6(8):1085–95.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Nanabala R, Sasikumar A, Joy A, Pillai MRA. Preparation of [177Lu]PSMA-617 using carrier added (CA) 177Lu for radionuclide therapy of prostate cancer. J Nucl Med Radiat Ther. 2016;7:306.CrossRefGoogle Scholar
  90. 90.
    Tagawa ST, Milowsky MI, Morris M, et al. Phase II study of lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate. Cancer Clin Cancer Res. 2013;19(18):5182–91.CrossRefPubMedGoogle Scholar
  91. 91.
    Rahbar K, Ahmadzadehfar H, Kratochwil C. German multicenter study investigating 177Lu-PSMA-617 radiology and therapy in advanced prostate cancer patients. J Nucl Med. 2017;58:85–90.CrossRefPubMedGoogle Scholar
  92. 92.
    Rahbar K, Bode A, Weckesser M, et al. Radioligand therapy with 177Lu-PSMA-617 as a novel therapeutic option in patients with metastatic castration resistant prostate. Cancer Clin Nucl Med. 2016;41:522–8.CrossRefPubMedGoogle Scholar
  93. 93.
    Kratochwil C, Giesel FL, Stefanova M. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med. 2016;57:1170–6.CrossRefPubMedGoogle Scholar
  94. 94.
    Afshar-Oromieh A, Babich JW, Kratochwil C. The rise of PSMA ligands for diagnosis and therapy of prostate cancer. Nucl Med. 2016;57:79S–89S.CrossRefGoogle Scholar
  95. 95.
    Heck MM, Retz M, D’Alessandria C, et al. Systemic radioligand therapy with 177Lu-PSMA-I&T in patients with metastatic castration-resistant prostate cancer. J Urol. 2016;196(2):382–91.CrossRefPubMedGoogle Scholar
  96. 96.
    Weineisen M, Schottelius M, Simecek J, et al. 68Ga- and 177Lu-labeled PSMA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med. 2015;56:1169–76.CrossRefPubMedGoogle Scholar
  97. 97.
    Chatalic KLS, Heskamp S, Konijnenberg M, et al. Towards personalized treatment of prostate cancer: PSMA I&T, a promising prostate-specific membrane antigen-targeted theranostic agent. Theranostics. 2016;6(6):849–61.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Barrio M, Fendler WP, Czernin J, Herrmann K. Prostate specific membrane antigen (PSMA) ligands for diagnosis and therapy of prostate cancer. Expert Rev. Mol Diagn. 2016;16(11):1177–88.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Nuclear Medicine UnitAOU Policlinico “G. Martino”MessinaItaly

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