• Robert PichlerEmail author
  • Johannes Wolfsgruber
  • Ferdinando Calabria
  • Orazio Schillaci
  • Andreas Dunzinger


Imaging prostate cancer and metastases either by morphologic radiological approach or nuclear medicine methods has not fulfilled the expectations of the clinicians until several years. PSMA—prostate-specific membrane antigen—which can be labeled with positron-emitting isotopes mostly 68Ga—changed this setting substantially. Prostate cancer is the most common tumor entity in men worldwide and the third leading cause of cancer-related death in men in Europe and the USA. Biochemical relapse is a frequent event after primary therapy. A large body of evidence is available for restaging of prostate cancer patients with biochemical recurrence. 68Ga-PSMA PET/CT demonstrates high detection rates in patients with biochemical recurrence of prostate cancer after primary radiation therapy as well as after radical prostatectomy. 68Ga-PSMA PET has also been used for radiotherapy planning. Compared to conventional CT, PSMA PET/CT had a remarkable impact on radiotherapeutic approach especially in postoperative patients. PSMA is an ideal structure for both imaging and targeted therapy for prostate cancer, therefore enabling a theranostic approach.


68Gallium Prostate-specific membrane antigen PSMA Prostate cancer PET PET/CT Biochemical relapse PSA Prostatectomy 





2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid






68Ga-prostate-specific membrane antigen


(1,4,7,10-tetraazacyclododecane-1-(1-carboxy-3-carbo-tertbutoxypropyl)-4,10 (carbotertbutoxymethyl)-7-acetamide)


Positron emission tomography/ computed tomography


Positron emission tomography/magnetic resonance imaging


Prostate-specific antigen


  1. 1.
    Nanabala R, Anees MK, Sasikumar A, et al. Preparation of [(68)Ga]PSMA-11 for PET-CT imaging using a manual synthesis module and organic matrix based (68)Ge/(68)Ga generator. Nucl Med Biol. 2016;43:463–9.CrossRefGoogle Scholar
  2. 2.
    Giovacchini G, Giovannini E, Riondato M, et al. PET/CT with 68Ga-PSMA in prostate cancer: radiopharmaceutical background and clinical implications. Curr Radiopharm. 2018;11:4–13.CrossRefGoogle Scholar
  3. 3.
    Afshar-Oromieh A, Babich JW, Kratochwil, et al. The rise of PSMA ligands for diagnosis and therapy of prostate cancer. J Nucl Med. 2016;57:79S–89S.CrossRefGoogle Scholar
  4. 4.
    Sheikhbahaei S, Afshar-Oromieh A, Eiber M, et al. Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging. Eur J Nucl Med Mol Imaging. 2017;44:2117–36.CrossRefGoogle Scholar
  5. 5.
    Lenzo NP, Meyrick D, Turner JH, et al. Review of gallium-68 PSMA PET/CT imaging in the management of prostate cancer. Diagnostics (Basel). 2018;11, 8Google Scholar
  6. 6.
    Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74.CrossRefGoogle Scholar
  7. 7.
    Jadvar H. PSMA PET in prostate cancer. J Nucl Med. 2015;56:1131–2.CrossRefGoogle Scholar
  8. 8.
    Salas Fragomeni RA, Amir T, Sheikhbahaei S, et al. Imaging of nonprostate cancers using PSMA-targeted radiotracers: rationale, current state of the field, and a call to arms. J Nucl Med. 2018;59:871–7.CrossRefGoogle Scholar
  9. 9.
    Ceci F, Uprimny C, Nilica B, et al. 68Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging. 2015;42:1284–94.CrossRefGoogle Scholar
  10. 10.
    Freedland SJ, Presti JC Jr, Amling CL, et al. Time trends in biochemical recurrence after radical prostatectomy: results of the SEARCH database. Urology. 2003;61:736–41.CrossRefGoogle Scholar
  11. 11.
    Rayn KN, Elnabawi YA, Sheth N. Clinical implications of PET/CT in prostate cancer management. Transl Androl Urol. 2018;7:844–54.CrossRefGoogle Scholar
  12. 12.
    Grubmüller B, Baltzer P, Hartenbach S, et al. PSMA ligand PET/MRI for primary prostate cancer: staging performance and clinical impact. Clin Cancer Res. 2018;24:6300–7.CrossRefGoogle Scholar
  13. 13.
    Afshar-Oromieh A, Avtzi E, Giesel FL, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209.CrossRefGoogle Scholar
  14. 14.
    Schwarzenboeck SM, Rauscher I, Bluemel C, et al. PSMA ligands for PET imaging of prostate cancer. J Nucl Med. 2017;58:1545–52.CrossRefGoogle Scholar
  15. 15.
    Perera M, Papa N, Roberts M, et al. Gallium-68 prostate-specific membrane antigen positron emission tomography in advanced prostate cancer-updated diagnostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-avid lesions: a systematic review and meta-analysis. Eur Urol. 2019;. [Epub ahead of print]Google Scholar
  16. 16.
    Müller J, Ferraro DA, Muehlematter UJ, et al. Clinical impact of 68Ga-PSMA-11 PET on patient management and outcome, including all patients referred for an increase in PSA level during the first year after its clinical introduction. Eur J Nucl Med Mol Imaging. 2019;6:889–900.CrossRefGoogle Scholar
  17. 17.
    Einspieler I, Rauscher I, Düwel C, et al. Detection efficacy of hybrid 68Ga-PSMA ligand PET/CT in prostate cancer patients with biochemical recurrence after primary radiation therapy defined by phoenix criteria. J Nucl Med. 2017;58:1081–7.CrossRefGoogle Scholar
  18. 18.
    Schmidt-Hegemann NS, Fendler WP, Ilhan H, et al. Outcome after PSMA PET/CT based radiotherapy in patients with biochemical persistence or recurrence after radical prostatectomy. Radiat Oncol. 2018;13:37.CrossRefGoogle Scholar
  19. 19.
    Calais J, Czernin J, Cao M, et al. 68Ga-PSMA-11 PET/CT mapping of prostate cancer biochemical recurrence after radical prostatectomy in 270 patients with a PSA level of less than 1.0 ng/mL: impact on salvage radiotherapy planning. J Nucl Med. 2018;59:230–7.CrossRefGoogle Scholar
  20. 20.
    Calais J, Czernin J, Fendler WP, et al. Randomized prospective phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT]. BMC Cancer. 2019;19:97.CrossRefGoogle Scholar
  21. 21.
    Heinzel A, Boghos D, Mottaghy FM, et al. 68Ga-PSMA PET/CT for monitoring response to 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2019;46:1054–62.CrossRefGoogle Scholar
  22. 22.
    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.CrossRefGoogle Scholar
  23. 23.
    Sathekge M, Bruchertseifer F, Knoesen O, et al. 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study. Eur J Nucl Med Mol Imaging. 2019;46:129–38.CrossRefGoogle Scholar
  24. 24.
    Kesavan M, Turner JH, Meyrick D, et al. Salvage radiopeptide therapy of advanced castrate-resistant prostate cancer with lutetium-177-labeled prostate-specific membrane antigen: efficacy and safety in routine practice. Cancer Biother Radiopharm. 2018;33:274–81.CrossRefGoogle Scholar
  25. 25.
    Afshar-Oromieh A, Zechmann CM, Malcher A, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:11–20.CrossRefGoogle Scholar
  26. 26.
    Lütje S, Heskamp S, Cornelissen AS, et al. PSMA ligands for radionuclide imaging and therapy of prostate cancer: clinical status. Theranostics. 2015;5:1388–401.CrossRefGoogle Scholar
  27. 27.
    Parent EE, Schuster DM. Update on 18F-fluciclovine PET for prostate cancer imaging. J Nucl Med. 2018;59:733–9.CrossRefGoogle Scholar
  28. 28.
    England JR, Paluch J, Ballas LK, et al. 18F-fluciclovine PET/CT detection of recurrent prostate carcinoma in patients with serum PSA ≤ 1 ng/mL after definitive primary treatment. Clin Nucl Med. 2019;44:e128–32.CrossRefGoogle Scholar
  29. 29.
    Andriole GL, Kostakoglu L, Chau A, et al. The impact of positron emission tomography with 18F-fluciclovine on the treatment of biochemical recurrence of prostate cancer: results from the LOCATE trial. J Urol. 2019;201:322–31.CrossRefGoogle Scholar
  30. 30.
    Koerber SA, Will L, Kratochwil C, et al. 68Ga-PSMA-11 PET/CT in primary and recurrent prostate carcinoma: implications for radiotherapeutic management in 121 patients. J Nucl Med. 2019;60(2):234–40.CrossRefGoogle Scholar
  31. 31.
    Rauscher I, Maurer T, Fendler WP, et al. (68)Ga-PSMA ligand PET/CT in patients with prostate cancer: how we review and report. Cancer Imaging. 2016;16:14.CrossRefGoogle Scholar
  32. 32.
    Afshar-Oromieh A, Sattler LP, Mier W, et al. The clinical impact of additional late PET/CT imaging with 68Ga-PSMA-11 (HBED-CC) in the diagnosis of prostate cancer. J Nucl Med. 2017;58:750–5.CrossRefGoogle Scholar
  33. 33.
    Krohn T, Verburg FA, Pufe T, et al. [(68)Ga]PSMA-HBED uptake mimicking lymph node metastasis in coeliac ganglia: an important pitfall in clinical practice. Eur J Nucl Med Mol Imaging. 2015;42:210–4.CrossRefGoogle Scholar
  34. 34.
    Strele-Trieb P, Dunzinger A, Sonnberger M, et al. Uptake of 68Ga-prostate-specific membrane antigen pet in adrenal gland: a potential pitfall. Clin Nucl Med. 2018;43:50–1.CrossRefGoogle Scholar
  35. 35.
    Calabria F, Gangemi V, Gullà D, et al. 64Cu-PSMA uptake in meningioma: a potential pitfall of a promising radiotracer. Rev Esp Med Nucl Imagen Mol. 2017;36:335–6.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Kesler M, Levine C, Hershkovitz D, et al. 68Ga-PSMA is a novel PET-CT tracer for imaging of hepatocellular carcinoma: a prospective pilot study. J Nucl Med. 2018;. [Epub ahead of print]Google Scholar
  37. 37.
    Backhaus P, Noto B, Avramovic N, et al. Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives. Eur J Nucl Med Mol Imaging. 2018;45:860–77.CrossRefGoogle Scholar
  38. 38.
    Nomura N, Pastorino S, Jiang P, et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int. 2014;14:26.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Robert Pichler
    • 1
    • 2
    • 3
    Email author
  • Johannes Wolfsgruber
    • 4
  • Ferdinando Calabria
    • 5
  • Orazio Schillaci
    • 6
    • 7
  • Andreas Dunzinger
    • 1
  1. 1.Institute of Nuclear MedicineKepler University HospitalLinzAustria
  2. 2.Institute of Nuclear MedicineGeneral Hospital SteyrSteyrAustria
  3. 3.Department of Radiology, Clinic of Nuclear MedicineMedical University GrazGrazAustria
  4. 4.Department of UrologyGeneral Hospital SteyrSteyrAustria
  5. 5.Department of Nuclear Medicine and Theranostics“Mariano Santo” HospitalCosenzaItaly
  6. 6.Department of Biomedicine and PreventionUniversity “Tor Vergata”RomeItaly
  7. 7.Department of Nuclear Medicine and Molecular ImagingIRCCS INM NeuromedPozzilliItaly

Personalised recommendations