Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Current use of PSMA–PET in prostate cancer management

Key Points

  • Prostate-specific membrane antigen (PSMA) is a promising and specific target for prostate cancer imaging

  • PSMA–PET imaging can add molecular information to multiparametric MRI and, therefore, delineate suspicious lesions for targeted biopsies, especially in patients whose biopsy samples are tumour-negative

  • PSMA–PET imaging shows increased specificity and sensitivity compared with current standard imaging (CT, MRI and bone scintigraphy) in patients with primary intermediate-risk or high-risk prostate cancer

  • PSMA–PET imaging improves detection of metastatic lesions even at low serum PSA values in biochemically recurrent prostate cancer

  • Enhanced detection of prostate cancer lesions might enable improved patient-tailored therapy planning and, therefore, lead to improved therapy outcomes

Abstract

Currently, the findings of imaging procedures used for detection or staging of prostate cancer depend on morphology of lymph nodes or bone metabolism and do not always meet diagnostic needs. Prostate-specific membrane antigen (PSMA), a transmembrane protein that has considerable overexpression on most prostate cancer cells, has gained increasing interest as a target molecule for imaging. To date, several small compounds for labelling PSMA have been developed and are currently being investigated as imaging probes for PET with the 68Ga-labelled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC being the most widely studied agent. 68Ga-PSMA–PET imaging in combination with multiparametric MRI (mpMRI) might provide additional molecular information on cancer localization within the prostate. In patients with primary prostate cancer of intermediate-risk to high-risk, PSMA-based imaging has been reported to improve detection of metastatic disease compared with CT or mpMRI, rendering additional cross-sectional imaging or bone scintigraphy unnecessary. Furthermore, in patients with biochemically recurrent prostate cancer, use of 68Ga-PSMA–PET imaging has been shown to increase detection of metastatic sites, even at low serum PSA values, compared with conventional imaging or PET examination with different tracers. Thus, although current knowledge is still limited and derived mostly from retrospective series, PSMA-based imaging holds great promise to improve prostate cancer management.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The structure of prostate-specific membrane antigen (PSMA), its binding sites for PSMA ligands and the most frequently used antibodies.
Figure 2: 68Ga-PSMA–PET–MRI of a 50-year-old patient who had a rising serum PSA value (16 ng/ml at imaging) and two tumour-negative previous biopsy samples.
Figure 3: 68Ga-PSMA–PET–CT of a 52-year-old patient with primary prostate cancer (serum PSA value of 19 ng/ml and Gleason score 7 at biopsy).
Figure 4: 68Ga-PSMA–PET–CT of a 73-year-old patient with recurrent prostate cancer after radical prostatectomy (initial Gleason score 9) and local salvage radiotherapy.
Figure 5: Imaging of 65-year-old patient with prostate cancer and diffuse bone metastases.
Figure 6: 68Ga-PSMA–PET–CT of a 74-year-old patient with recurrent prostate cancer (initial Gleason score 7) after radical prostatectomy and local salvage radiotherapy with rising serum PSA value (1.76 ng/ml at the time of assessment).

Similar content being viewed by others

References

  1. Torre, L. A. et al. Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87–108 (2015).

    PubMed  Google Scholar 

  2. American Urological Association. Guideline for the management of clinically localized prostate cancer (2007). [online], (2007).

  3. European Association of Urology. Guidelines on Prostate Cancer. http://uroweb.org/guideline/prostate-cancer/ (2015).

  4. Barentsz, J. O. et al. ESUR prostate MR guidelines 2012. Eur. Radiol. 22, 746–757 (2012).

    PubMed  PubMed Central  Google Scholar 

  5. Baco, E. et al. Magnetic resonance imaging-transectal ultrasound image-fusion biopsies accurately characterize the index tumor: correlation with step-sectioned radical prostatectomy specimens in 135 patients. Eur. Urol. 67, 787–794 (2015).

    PubMed  Google Scholar 

  6. Valerio, M. et al. Detection of clinically significant prostate cancer using magnetic resonance imaging-ultrasound fusion targeted biopsy: a systematic review. Eur. Urol. 68, 8–19 (2015).

    PubMed  Google Scholar 

  7. Dianat, S. S., Carter, H. B. & Macura, K. J. Performance of multiparametric magnetic resonance imaging in the evaluation and management of clinically low-risk prostate cancer. Urol. Oncol. 32, 39.e1–39.e10 (2014).

    Google Scholar 

  8. Reisaeter, L. A. et al. 1.5-T multiparametric MRI using PI-RADS: a region by region analysis to localize the index-tumor of prostate cancer in patients undergoing prostatectomy. Acta Radiol. 56, 500–511 (2015).

    PubMed  Google Scholar 

  9. Hoeks, C. M. et al. Transition zone prostate cancer: detection and localization with 3-T multiparametric MR imaging. Radiology 266, 207–217 (2013).

    PubMed  Google Scholar 

  10. Schimmoller, L. et al. MR-sequences for prostate cancer diagnostics: validation based on the PI-RADS scoring system and targeted MR-guided in-bore biopsy. Eur. Radiol. 24, 2582–2589 (2014).

    PubMed  Google Scholar 

  11. National Comprehensive Cancer Network. Prostate cancer. ">[online], (2015).

  12. Umbehr, M. H., Muntener, M., Hany, T., Sulser, T. & Bachmann, L. M. The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur. Urol. 64, 106–117 (2013).

    PubMed  Google Scholar 

  13. Yu, C. Y., Desai, B., Ji, L., Groshen, S. & Jadvar, H. Comparative performance of PET tracers in biochemical recurrence of prostate cancer: a critical analysis of literature. Am. J. Nucl. Med. Mol. Imaging 4, 580–601 (2014).

    PubMed  PubMed Central  Google Scholar 

  14. Souvatzoglou, M. et al. The sensitivity of [11C]choline PET/CT to localize prostate cancer depends on the tumor configuration. Clin. Cancer Res. 17, 3751–3759 (2011).

    PubMed  Google Scholar 

  15. Brogsitter, C., Zophel, K. & Kotzerke, J. 18F-choline, 11C-choline and 11C-acetate PET/CT: comparative analysis for imaging prostate cancer patients. Eur. J. Nucl. Med. Mol. Imaging 40, S18–S27 (2013).

    PubMed  Google Scholar 

  16. Evangelista, L., Guttilla, A., Zattoni, F., Muzzio, P. C. & Zattoni, F. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Eur. Urol. 63, 1040–1048 (2013).

    PubMed  Google Scholar 

  17. Beresford, M. J., Gillatt, D., Benson, R. J. & Ajithkumar, T. A systematic review of the role of imaging before salvage radiotherapy for post-prostatectomy biochemical recurrence. Clin. Oncol. (R. Coll. Radiol.) 22, 46–55 (2010).

    CAS  Google Scholar 

  18. Krause, B. J. et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 35, 18–23 (2008).

    CAS  PubMed  Google Scholar 

  19. Schoder, H. et al. 2-[18F]fluoro-2-deoxyglucose positron emission tomography for the detection of disease in patients with prostate-specific antigen relapse after radical prostatectomy. Clin. Cancer Res. 11, 4761–4769 (2005).

    PubMed  Google Scholar 

  20. Afshar-Oromieh, A., Haberkorn, U., Eder, M., Eisenhut, M. & Zechmann, C. M. [68Ga]gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH. Eur. J. Nuclear Med. Mol. Imaging 39, 1085–1086 (2012).

    CAS  Google Scholar 

  21. Leek, J. et al. Prostate-specific membrane antigen: evidence for the existence of a second related human gene. Br. J. Cancer 72, 583–588 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. O'Keefe, D. S. et al. Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. Biochim. Biophys. Acta 1443, 113–127 (1998).

    CAS  PubMed  Google Scholar 

  23. DeMarzo, A. M., Nelson, W. G., Isaacs, W. B. & Epstein, J. I. Pathological and molecular aspects of prostate cancer. Lancet 361, 955–964 (2003).

    CAS  PubMed  Google Scholar 

  24. Grauer, L. S. et al. Identification, purification, and subcellular localization of prostate-specific membrane antigen PSM′ protein in the LNCaP prostatic carcinoma cell line. Cancer Res. 58, 4787–4789 (1998).

    CAS  PubMed  Google Scholar 

  25. Heston, W. D. Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase. Urology 49, 104–112 (1997).

    CAS  PubMed  Google Scholar 

  26. Huang, E., Teh, B. S., Mody, D. R., Carpenter, L. S. & Butler, E. B. Prostate adenocarcinoma presenting with inguinal lymphadenopathy. Urology 61, 463 (2003).

    PubMed  Google Scholar 

  27. Wu, L. M., Xu, J. R., Ye, Y. Q., Lu, Q. & Hu, J. N. The clinical value of diffusion-weighted imaging in combination with T2-weighted imaging in diagnosing prostate carcinoma: a systematic review and meta-analysis. AJR Am. J. Roentgenol. 199, 103–110 (2012).

    PubMed  Google Scholar 

  28. Birtle, A. J. et al. Tumour markers for managing men who present with metastatic prostate cancer and serum prostate-specific antigen levels of <10 ng/mL. BJU Int. 96, 303–307 (2005).

    PubMed  Google Scholar 

  29. Evans, M. J. et al. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc. Natl Acad. Sci. USA 108, 9578–9582 (2011).

    CAS  PubMed  Google Scholar 

  30. Chang, S. S. et al. Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin. Cancer Res. 5, 2674–2681 (1999).

    CAS  PubMed  Google Scholar 

  31. Chang, S. S. et al. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res. 59, 3192–3198 (1999).

    CAS  PubMed  Google Scholar 

  32. Chang, S. S., Reuter, V. E., Heston, W. D. & Gaudin, P. B. Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen. Urology 57, 801–805 (2001).

    CAS  PubMed  Google Scholar 

  33. Haffner, M. C. et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum. Pathol. 40, 1754–1761 (2009).

    CAS  PubMed  Google Scholar 

  34. Samplaski, M. K., Heston, W., Elson, P., Magi-Galluzzi, C. & Hansel, D. E. Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature. Mod. Pathol. 24, 1521–1529 (2011).

    CAS  PubMed  Google Scholar 

  35. Silver, D. A., Pellicer, I., Fair, W. R., Heston, W. D. & Cordon-Cardo, C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin. Cancer Res. 3, 81–85 (1997).

    CAS  PubMed  Google Scholar 

  36. Carter, R. E., Feldman, A. R. & Coyle, J. T. Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc. Natl Acad. Sci. USA 93, 749–753 (1996).

    CAS  PubMed  Google Scholar 

  37. Robinson, M. B., Blakely, R. D., Couto, R. & Coyle, J. T. Hydrolysis of the brain dipeptide N-acetyl-l-aspartyl-l-glutamate. J. Biol. Chem. 262, 14498–14506 (1987).

    CAS  PubMed  Google Scholar 

  38. Rowe, S. P. et al. Detection of 18F-FDG PET/CT occult lesions with 18F-DCFPyL PET/CT in a patient with metastatic renal cell carcinoma. Clin. Nucl. Med. 41, 83–85 (2015).

    Google Scholar 

  39. Rowe, S. P. et al. Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted F-DCFPyL PET/CT. Ann. Nucl. Med. 29, 877–882 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Verburg, F. A., Krohn, T., Heinzel, A., Mottaghy, F. M. & Behrendt, F. F. First evidence of PSMA expression in differentiated thyroid cancer using [68Ga]PSMA-HBED-CC PET/CT. Eur. J. Nucl. Med. Mol. Imaging 42, 1622–1623 (2015).

    PubMed  Google Scholar 

  41. Krohn, T. et al. [68Ga]PSMA-HBED uptake mimicking lymph node metastasis in coeliac ganglia: an important pitfall in clinical practice. Eur. J. Nucl. Med. Mol. Imaging 42, 210–214 (2015).

    PubMed  Google Scholar 

  42. Schwenck, J. et al. In vivo visualization of prostate-specific membrane antigen in glioblastoma. Eur. J. Nucl. Med. Mol. Imaging 42, 170–171 (2015).

    PubMed  Google Scholar 

  43. Rischpler, C., Maurer, T., Schwaiger, M. & Eiber, M. Intense PSMA-expression using 68Ga-PSMA PET/CT in a paravertebral schwannoma mimicking prostate cancer metastasis. Eur. J. Nucl. Med. Mol. Imaging 43, 193–194 (2016).

    PubMed  Google Scholar 

  44. Ghosh, A. & Heston, W. D. W. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J. Cell. Biochem. 91, 528–539 (2004).

    CAS  PubMed  Google Scholar 

  45. Schülke, N. et al. The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy. Proc. Natl Acad. Sci. USA 100, 12590–12595 (2003).

    PubMed  Google Scholar 

  46. Commandeur, L. C. & Parsons, J. R. Degradation of halogenated aromatic compounds. Biodegradation 1, 207–220 (1990).

    CAS  PubMed  Google Scholar 

  47. Bostwick, D. G., Pacelli, A., Blute, M., Roche, P. & Murphy, G. P. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 82, 2256–2261 (1998).

    CAS  PubMed  Google Scholar 

  48. Mannweiler, S. et al. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol. Oncol. Res. 15, 167–172 (2009).

    CAS  PubMed  Google Scholar 

  49. Troyer, J. K., Beckett, M. L. & Wright, G. L. Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int. J. Cancer. 62, 552–558 (1995).

    CAS  PubMed  Google Scholar 

  50. Maurer, T. et al. Prostate-specific membrane antigen-radioguided surgery for metastatic lymph nodes in prostate cancer. Eur. Urol. 68, 530–534 (2015).

    PubMed  Google Scholar 

  51. Chang, S. S. Overview of prostate-specific membrane antigen. Rev. Urol. 6, S13–S18 (2004).

    PubMed  PubMed Central  Google Scholar 

  52. Rajasekaran, S. A. et al. A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. Mol. Biol. Cell 14, 4835–4845 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Liu, H. et al. Constitutive and antibody-induced internalization of prostate-specific membrane antigen. Cancer Res. 58, 4055–4060 (1998).

    CAS  PubMed  Google Scholar 

  54. Eder, M. et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug. Chem. 23, 688–697 (2012).

    CAS  PubMed  Google Scholar 

  55. Ghosh, A. & Heston, W. D. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J. Cell. Biochem. 91, 528–539 (2004).

    CAS  PubMed  Google Scholar 

  56. Troyer, J. K., Beckett, M. L. & Wright, G. L. Location of prostate-specific membrane antigen in the LNCaP prostate carcinoma cell line. Prostate 30, 232–242 (1997).

    CAS  PubMed  Google Scholar 

  57. Tagawa, S. T. et al. Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate cancer. Cancer 116, 1075–1083 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Elsässer-Beile, U. et al. PET imaging of prostate cancer xenografts with a highly specific antibody against the prostate-specific membrane antigen. J. Nuclear Med. 50, 606–611 (2009).

    Google Scholar 

  59. Holland, J. P. et al. 89Zr-DFO-J591 for immunoPET of prostate-specific membrane antigen expression in vivo. J. Nucl. Med. 51, 1293–1300 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Wiehr, S. et al. Pharmacokinetics and PET imaging properties of two recombinant anti-PSMA antibody fragments in comparison to their parental antibody. Prostate 74, 743–755 (2014).

    CAS  PubMed  Google Scholar 

  61. Luthi-Carter, R., Barczak, A. K., Speno, H. & Coyle, J. T. Molecular characterization of human brain N-acetylated α-linked acidic dipeptidase (NAALADase). J. Pharmacol. Exp. Ther. 286, 1020–1025 (1998).

    CAS  PubMed  Google Scholar 

  62. Tiffany, C. W., Lapidus, R. G., Merion, A., Calvin, D. C. & Slusher, B. S. Characterization of the enzymatic activity of PSM: comparison with brain NAALADase. Prostate 39, 28–35 (1999).

    CAS  PubMed  Google Scholar 

  63. Wang, H. et al. Bioisosterism of urea-based GCPII inhibitors: synthesis and structure–activity relationship studies. Bioorg. Med. Chem. Lett. 20, 392–397 (2010).

    CAS  PubMed  Google Scholar 

  64. Mease, R. C., Foss, C. A. & Pomper, M. G. PET imaging in prostate cancer: focus on prostate-specific membrane antigen. Curr. Top. Med. Chem. 13, 951–962 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Foss, C. A. et al. Radiolabeled small-molecule ligands for prostate-specific membrane antigen: in vivo imaging in experimental models of prostate cancer. Clin. Cancer Res. 11, 4022–4028 (2005).

    CAS  PubMed  Google Scholar 

  66. Hillier, S. M. et al. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res. 69, 6932–6940 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Maresca, K. P. et al. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J. Med. Chem. 52, 347–357 (2009).

    CAS  PubMed  Google Scholar 

  68. Kularatne, S. A., Zhou, Z., Yang, J., Post, C. B. & Low, P. S. Design, synthesis, and preclinical evaluation of prostate-specific membrane antigen targeted 99mTc-radioimaging agents. Mol. Pharm. 6, 790–800 (2009).

    CAS  PubMed  Google Scholar 

  69. Lu, G. et al. Synthesis and SAR of 99mTc/Re-labeled small molecule prostate specific membrane antigen inhibitors with novel polar chelates. Bioorg. Med. Chem. Lett. 23, 1557–1563 (2013).

    CAS  PubMed  Google Scholar 

  70. Chen, Y. et al. 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. 17, 7645–7653 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Rowe, S. P. et al. 18F-DCFBC PET/CT for PSMA-based detection and characterization of primary prostate cancer. J. Nucl. Med. 56, 1003–1010 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Banerjee, S. R. et al. A modular strategy to prepare multivalent inhibitors of prostate-specific membrane antigen (PSMA). Oncotarget 2, 1244–1253 (2011).

    PubMed  PubMed Central  Google Scholar 

  73. Afshar-Oromieh, A. et al. The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 42, 197–209 (2015).

    CAS  PubMed  Google Scholar 

  74. Afshar-Oromieh, A. et al. 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 41, 11–20 (2014).

    CAS  PubMed  Google Scholar 

  75. Afshar-Oromieh, A. et al. PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 40, 1629–1630 (2013).

    PubMed  Google Scholar 

  76. Weineisen, M., Simecek, J., Schottelius, M., Schwaiger, M. & Wester, H.-J. Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. EJNMMI Res. 4, 63 (2014).

    PubMed  PubMed Central  Google Scholar 

  77. Afshar-Oromieh, A. et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur. J. Nucl. Med. Mol. Imaging 40, 486–495 (2013).

    CAS  PubMed  Google Scholar 

  78. Roesch, F. & Riss, P. J. The renaissance of the 68Ge/68Ga radionuclide generator initiates new developments in 68Ga radiopharmaceutical chemistry. Curr. Top. Med. Chem. 10, 1633–1668 (2010).

    CAS  PubMed  Google Scholar 

  79. Schottelius, M., Wirtz, M., Eiber, M., Maurer, T. & Wester, H. J. [111In]PSMA-I&T: expanding the spectrum of PSMA-I&T applications towards SPECT and radioguided surgery. EJNMMI Res. 5, 68 (2015).

    PubMed  PubMed Central  Google Scholar 

  80. Weineisen, M. 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. 56, 1169–1176 (2015).

    CAS  PubMed  Google Scholar 

  81. Weineisen, M., Simecek, J., Schottelius, M., Schwaiger, M. & Wester, H. J. Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. EJNMMI Res. 4, 63 (2014).

    PubMed  PubMed Central  Google Scholar 

  82. Benešová, M. et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J. Nucl. Med. 56, 914–920 (2015).

    PubMed  Google Scholar 

  83. Afshar-Oromieh, A. et al. The novel 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. 56, 1697–1705 (2015).

    CAS  PubMed  Google Scholar 

  84. Delker, A. et al. Dosimetry for Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 43, 42–51 (2015).

    PubMed  Google Scholar 

  85. Ahmadzadehfar, H. et al. Early side effects and first results of radioligand therapy with 177Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study. EJNMMI Res. 5, 114 (2015).

    PubMed  Google Scholar 

  86. Dietlein, M. et al. Comparison of [18F]DCFPyL and [68Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol. Imaging Biol. 17, 575–584 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Malik, N. et al. Radiofluorination of PSMA-HBED via Al18F2+ chelation and biological evaluations in vitro. Mol. Imaging Biol. 17, 777–785 (2015).

    CAS  PubMed  Google Scholar 

  88. Mease, R. C. et al. N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-l-cysteine, [18F]DCFBC: a new imaging probe for prostate cancer. Clin. Cancer Res. 14, 3036–3043 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Cho, S. Y. et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J. Nucl. Med. 53, 1883–1891 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Szabo, Z. et al. Initial evaluation of [18F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol. Imaging Biol. 17, 565–574 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Futterer, J. J. et al. Prostate cancer localization with dynamic contrast-enhanced MR imaging and proton MR spectroscopic imaging. Radiology 241, 449–458 (2006).

    PubMed  Google Scholar 

  92. Lim, H. K., Kim, J. K., Kim, K. A. & Cho, K. S. Prostate cancer: apparent diffusion coefficient map with T2-weighted images for detection — a multireader study. Radiology 250, 145–151 (2009).

    PubMed  Google Scholar 

  93. Sciarra, A. et al. Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy. Clin. Cancer Res. 16, 1875–1883 (2010).

    CAS  PubMed  Google Scholar 

  94. Tan, C. H., Wei, W., Johnson, V. & Kundra, V. Diffusion-weighted MRI in the detection of prostate cancer: meta-analysis. AJR Am. J. Roentgenol. 199, 822–829 (2012).

    PubMed  PubMed Central  Google Scholar 

  95. Issa, B. In vivo measurement of the apparent diffusion coefficient in normal and malignant prostatic tissues using echo-planar imaging. J. Magn. Reson. Imaging 16, 196–200 (2002).

    PubMed  Google Scholar 

  96. Jacobs, M. A., Ouwerkerk, R., Petrowski, K. & Macura, K. J. Diffusion-weighted imaging with apparent diffusion coefficient mapping and spectroscopy in prostate cancer. Top. Magn. Reson. Imaging 19, 261–272 (2008).

    PubMed  PubMed Central  Google Scholar 

  97. Manenti, G. et al. In vivo measurement of the apparent diffusion coefficient in normal and malignant prostatic tissue using thin-slice echo-planar imaging. Radiol. Med. 111, 1124–1133 (2006).

    CAS  PubMed  Google Scholar 

  98. Puech, P. et al. Dynamic contrast-enhanced-magnetic resonance imaging evaluation of intraprostatic prostate cancer: correlation with radical prostatectomy specimens. Urology 74, 1094–1099 (2009).

    PubMed  Google Scholar 

  99. Chen, Y. J. et al. Washout gradient in dynamic contrast-enhanced MRI is associated with tumor aggressiveness of prostate cancer. J. Magn. Reson. Imaging 36, 912–919 (2012).

    PubMed  Google Scholar 

  100. Oto, A. et al. Diffusion-weighted and dynamic contrast-enhanced MRI of prostate cancer: correlation of quantitative MR parameters with Gleason score and tumor angiogenesis. AJR Am. J. Roentgenol. 197, 1382–1390 (2011).

    PubMed  Google Scholar 

  101. Yerram, N. K. et al. Low suspicion lesions on multiparametric magnetic resonance imaging predict for the absence of high-risk prostate cancer. BJU Int. 110, E783–E788 (2012).

    PubMed  Google Scholar 

  102. Souvatzoglou, M. et al. PET/MR in prostate cancer: technical aspects and potential diagnostic value. Eur. J. Nucl. Med. Mol. Imaging 40, S79–S88 (2013).

    PubMed  Google Scholar 

  103. Souvatzoglou, M. et al. Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 40, 1486–1499 (2013).

    CAS  PubMed  Google Scholar 

  104. Eiber, M. et al. 68Ga-PSMA PET/MR with multimodality image analysis for primary prostate cancer. Abdom. Imaging 40, 1769–1771 (2014).

    Google Scholar 

  105. Eiber, M. et al. Simultaneous 68Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur. Urol.(in the press).

  106. Storz, E. et al. PSMA-PET/MRI-guided transrectal fusion biopsy for the detection of prostate cancer. Eur. Urol. Suppl. 14, E217 (2015).

    Google Scholar 

  107. Zettinig, O. et al. Multimodal image-guided prostate fusion biopsy based on automatic deformable registration. Int. J. Comput. Assist. Radiol. Surg. 10, 1997–2007 (2015).

    PubMed  Google Scholar 

  108. Maurer, T. et al. Diagnostic efficacy of 68Gallium-PSMA-PET compared to conventional imaging in lymph node staging of of 130 consecutive patients with intermediate to high-risk prostate cancer. J. Urol. http://dx.doi.org/10.1016/j.juro.2015.12.025 (2015).

  109. Lecouvet, F. E. et al. Can whole-body magnetic resonance imaging with diffusion-weighted imaging replace Tc 99m bone scanning and computed tomography for single-step detection of metastases in patients with high-risk prostate cancer? Eur. Urol. 62, 68–75 (2012).

    PubMed  Google Scholar 

  110. Heesakkers, R. A. et al. MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study. Lancet Oncol. 9, 850–856 (2008).

    CAS  PubMed  Google Scholar 

  111. Hovels, A. M. et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin. Radiol. 63, 387–395 (2008).

    CAS  PubMed  Google Scholar 

  112. Akduman, E. I. et al. Comparison between malignant and benign abdominal lymph nodes on diffusion-weighted imaging. Acad. Radiol. 15, 641–646 (2008).

    PubMed  Google Scholar 

  113. Eiber, M. et al. Preliminary results for characterization of pelvic lymph nodes in patients with prostate cancer by diffusion-weighted MR-imaging. Invest. Radiol. 45, 15–23 (2010).

    PubMed  Google Scholar 

  114. Kim, J. K., Kim, K. A., Park, B. W., Kim, N. & Cho, K. S. Feasibility of diffusion-weighted imaging in the differentiation of metastatic from nonmetastatic lymph nodes: early experience. J. Magn. Reson. Imaging 28, 714–719 (2008).

    PubMed  Google Scholar 

  115. Jadvar, H. Imaging evaluation of prostate cancer with 18F-fluorodeoxyglucose PET/CT: utility and limitations. Eur. J. Nucl. Med. Mol. Imaging 40, S5–S10 (2013).

    PubMed  Google Scholar 

  116. Mohsen, B. et al. Application of C-11-acetate positron-emission tomography (PET) imaging in prostate cancer: systematic review and meta-analysis of the literature. BJU Int. 112, 1062–1072 (2013).

    CAS  PubMed  Google Scholar 

  117. Pinaquy, J. B. et al. Comparative effectiveness of [18F]-fluorocholine PET-CT and pelvic MRI with diffusion-weighted imaging for staging in patients with high-risk prostate cancer. Prostate 75, 323–331 (2015).

    CAS  PubMed  Google Scholar 

  118. Schumacher, M. C., Radecka, E., Hellstrom, M., Jacobsson, H. & Sundin, A. [11C]acetate positron emission tomography-computed tomography imaging of prostate cancer lymph-node metastases correlated with histopathological findings after extended lymphadenectomy. Scand. J. Urol. 49, 35–42 (2015).

    CAS  PubMed  Google Scholar 

  119. de Jong, I. J., Pruim, J., Elsinga, P. H., Vaalburg, W. & Mensink, H. J. Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-choline PET. J. Nucl. Med. 44, 331–335 (2003).

    PubMed  Google Scholar 

  120. Kotzerke, J. et al. Experience with carbon-11 choline positron emission tomography in prostate carcinoma. Eur. J. Nucl. Med. 27, 1415–1419 (2000).

    CAS  PubMed  Google Scholar 

  121. Beheshti, M. et al. 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology 254, 925–933 (2010).

    PubMed  Google Scholar 

  122. Kjolhede, H. et al. 18F-fluorocholine PET/CT compared with extended pelvic lymph node dissection in high-risk prostate cancer. World J. Urol. 32, 965–970 (2014).

    CAS  PubMed  Google Scholar 

  123. Chakraborty, P. S., Kumar, R., Tripathi, M., Das, C. J. & Bal, C. Detection of brain metastasis with 68Ga-labeled PSMA ligand PET/CT: a novel radiotracer for imaging of prostate carcinoma. Clin. Nucl. Med. 40, 328–329 (2015).

    PubMed  Google Scholar 

  124. Kabasakal, L. et al. Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging. Nucl. Med. Commun. 36, 582–587 (2015).

    CAS  PubMed  Google Scholar 

  125. Maurer, T. et al. Positron emission tomography/magnetic resonance imaging with 68Gallium-labeled ligand of prostate-specific membrane antigen: promising novel option in prostate cancer imaging? Int. J. Urol. 21, 1286–1288 (2014).

    CAS  PubMed  Google Scholar 

  126. Pfister, D. et al. Early salvage radiotherapy following radical prostatectomy. Eur. Urol. 65, 1034–1043 (2014).

    PubMed  Google Scholar 

  127. King, C. R. The timing of salvage radiotherapy after radical prostatectomy: a systematic review. Int. J. Radiat. Oncol. Biol. Phys. 84, 104–111 (2012).

    PubMed  Google Scholar 

  128. Rouviere, O., Vitry, T. & Lyonnet, D. Imaging of prostate cancer local recurrences: why and how? Eur. Radiol 20, 1254–1266 (2010).

    PubMed  Google Scholar 

  129. Eiber, M. et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J. Nucl. Med. 56, 668–674 (2015).

    PubMed  Google Scholar 

  130. Castellucci, P. et al. Is there a role for 11C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml? Eur. J. Nucl. Med. Mol. Imaging 38, 55–63 (2011).

    PubMed  Google Scholar 

  131. Castellucci, P. & Picchio, M. 11C-choline PET/CT and PSA kinetics. Eur. J. Nucl. Med. Mol. Imaging 40, S36–S40 (2013).

    PubMed  Google Scholar 

  132. Graute, V. et al. Relationship between PSA kinetics and [18F]fluorocholine PET/CT detection rates of recurrence in patients with prostate cancer after total prostatectomy. Eur. J. Nucl. Med. Mol. Imaging 39, 271–282 (2012).

    CAS  PubMed  Google Scholar 

  133. Maurer, T. et al. PET imaging with 68Gallium-labelled ligand of prostate-specific membrane antigen (68Ga-HBED-PSMA) for staging of biochemical recurrent prostate cancer after radical prostatectomy. J. Clin. Oncol. 33 (Suppl.),5023 (2015).

    Google Scholar 

  134. US National Library of Medicine. ClinicalTrials.gov [online], (2015).

  135. US National Library of Medicine. ClinicalTrials.gov [online], (2015).

  136. US National Library of Medicine. ClinicalTrials.gov [online], (2015).

  137. EU Clinical Trials Register. clinicaltrialsregister.eu [online], (2015).

Download references

Author information

Authors and Affiliations

Authors

Contributions

T.M. and M.E. contributed equally to the manuscript, researched data for and wrote the article. All authors made a substantial contribution to discussions of content and edited the manuscript before submission.

Corresponding author

Correspondence to Tobias Maurer.

Ethics declarations

Competing interests

T.M. declares a familial association with Celgene® (Celgene Corporation, USA); grants or funding from Acelity® (KCI Licensing, Inc.), Bayer® (Bayer Aktiengesellschaft, Germany) and Takeda Oncology® (Takeda Pharmaceutical Company Limited, Japan); consultation for DLR® (Deutsches Luft-und Raumfahrtzentrum, Germany) and honoraria from Astellas® (Astellas US LLC, USA), Janssen Cilag (Johnson & Johnson, USA) and Sanofi® (Sanofi Corporation, France). M.E. declares grants or funding from Bayer® and honoraria Astellas® and Janssen Cilag. M.S. and J.E.G. declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maurer, T., Eiber, M., Schwaiger, M. et al. Current use of PSMA–PET in prostate cancer management. Nat Rev Urol 13, 226–235 (2016). https://doi.org/10.1038/nrurol.2016.26

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2016.26

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing