Advertisement

68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour

  • Christian Uprimny
  • Alexander Stephan Kroiss
  • Clemens Decristoforo
  • Josef Fritz
  • Elisabeth von Guggenberg
  • Dorota Kendler
  • Lorenza Scarpa
  • Gianpaolo di Santo
  • Llanos Geraldo Roig
  • Johanna Maffey-Steffan
  • Wolfgang Horninger
  • Irene Johanna Virgolini
Original Article

Abstract

Purpose

Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by 68Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of 68Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related 68Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level.

Methods

Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6–10; median PSA: 9.7 ng/ml) referred for 68Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax). The SUVmax of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUVmax of the primary tumour was assessed in relation to both PSA level and GS.

Results

Eighty-two patients (91.1%) demonstrated pathologic tracer accumulation in the primary tumour that exceeded physiologic tracer uptake in normal prostate tissue (median SUVmax: 12.5 vs. 3.9). Tumours with GS of 6, 7a (3+4) and 7b (4+3) showed significantly lower 68Ga-PSMA-11 uptake, with median SUVmax of 5.9, 8.3 and 8.2, respectively, compared to patients with GS >7 (median SUVmax: 21.2; p < 0.001). PC patients with PSA ≥10.0 ng/ml exhibited significantly higher uptake than those with PSA levels <10.0 ng/ml (median SUVmax: 17.6 versus 7.7; p < 0.001). In 24 patients (26.7%), 82 lymph nodes with pathologic tracer accumulation consistent with metastases were detected (median SUVmax: 10.6). Eleven patients (12.2%) revealed 55 pathologic osseous lesions suspicious for bone metastases (median SUVmax: 11.6).

Conclusions

The GS and PSA level correlated with the intensity of tracer accumulation in the primary tumours of PC patients on 68Ga-PSMA-11 PET/CT. As PC tumours with GS 6+7 and patients with PSA values ≤10 ng/ml showed significantly lower 68Ga-PSMA-11 uptake, 68Ga-PSMA-11 PET/CT should be preferentially applied for primary staging of PC in patients with GS >7 or PSA levels ≥10 ng/ml.

Keywords

68Ga-PSMA-11 PET/CT Prostate cancer Primary staging 

Notes

Acknowledgments

We want to express our gratitude to all the members of our PET staff for their contribution in performing this study.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All patients published in this manuscript provided written informed consent.

References

  1. 1.
    Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2016. doi: 10.1016/j.eururo.2016.08.003.Google Scholar
  2. 2.
    Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer: Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014;65(1):124–37.CrossRefPubMedGoogle Scholar
  3. 3.
    de Rooij M, Hamoen EH, Witjes JA, Barentsz JO, Rovers MM. Accuracy of magnetic resonance imaging for local staging of prostate cancer: a diagnostic meta-analysis. Eur Urol. 2016;70(2):233–45. doi: 10.1016/j.eururo.2015.07.029.CrossRefPubMedGoogle Scholar
  4. 4.
    Zacho HD, Barsi T, Mortensen JC, Bertelsen H, Petersen LJ. Validation of contemporary guidelines for bone scintigraphy in prostate cancer staging: a prospective study in patients undergoing radical prostatectomy. Scand J Urol. 2016;50(1):29–32.CrossRefPubMedGoogle Scholar
  5. 5.
    Beheshti M, Langsteger W. PET imaging of prostate cancer using radiolabeled choline. PET Clin. 2009;4(2):173–84. doi: 10.1016/j.cpet.2009.06.003.CrossRefPubMedGoogle Scholar
  6. 6.
    Evangelista L, Briganti A, Fanti S, Joniau S, Reske S, Schiavina R, et al. New clinical indications for (18)F/(11)C-choline, new tracers for positron emission tomography and a promising hybrid device for prostate cancer staging: a systematic review of the literature. Clin Nucl Med. 2016;41(9):746.CrossRefPubMedGoogle Scholar
  7. 7.
    Fanti S, Minozzi S, Castellucci P, Balduzzi S, Herrmann K, Krause BJ, et al. PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data. Eur J Nucl Med Mol Imaging. 2016;43(1):55–69. doi: 10.1007/s00259-015-3202-7.CrossRefPubMedGoogle Scholar
  8. 8.
    Ceci F, Herrmann K, Castellucci P, Graziani T, Bluemel C, Schiavina R, et al. Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial. Eur J Nucl Med Mol Imaging. 2014;41(12):2222–31. doi: 10.1007/s00259-014-2872-x.CrossRefPubMedGoogle Scholar
  9. 9.
    Picchio M, Briganti A, Fanti S, Heidenreich A, Krause BJ, Messa C, et al. The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol. 2011;59(1):51–60. doi: 10.1016/j.eururo.2010.09.004.CrossRefPubMedGoogle Scholar
  10. 10.
    Kitajima K, Murphy RC, Nathan MA, Sugimura K. Update on positron emission tomography for imaging of prostate cancer. Int J Urol. 2014;21(1):12–23. doi: 10.1111/iju.12250.CrossRefPubMedGoogle Scholar
  11. 11.
    Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, 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. 2013;40(4):486–95. doi: 10.1007/s00259-012-2298-2.CrossRefPubMedGoogle Scholar
  12. 12.
    Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, 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(2):197–209. doi: 10.1007/s00259-014-2949-6.CrossRefPubMedGoogle Scholar
  13. 13.
    Ceci F, Uprimny C, Nilica B, Geraldo L, Kendler D, Kroiss A, et al. (68)Ga-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(8):1284–94. doi: 10.1007/s00259-015-3078-6.CrossRefPubMedGoogle Scholar
  14. 14.
    Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. 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. doi: 10.2967/jnumed.115.154153.CrossRefPubMedGoogle Scholar
  15. 15.
    Lindenberg L, Choyke P, Dahut W. Prostate cancer imaging with novel PET tracers. Curr Urol Rep. 2016;17(3):18. doi: 10.1007/s11934-016-0575-5.CrossRefPubMedGoogle Scholar
  16. 16.
    Jadvar H. PSMA PET, in Prostate Cancer. J Nucl Med. 2015;56(8):1131–2. doi: 10.2967/jnumed.115.157339.CrossRefPubMedGoogle Scholar
  17. 17.
    Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive 68Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016. doi: 10.1016/j.eururo.2016.06.021.Google Scholar
  18. 18.
    Banerjee SR, Pullambhatla M, Byun Y, Nimmagadda S, Green G, Fox JJ, et al. 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer. J Med Chem. 2010;53(14):5333–41.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;91(3):528–39.CrossRefPubMedGoogle Scholar
  20. 20.
    Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52(4):637–40.CrossRefPubMedGoogle Scholar
  21. 21.
    Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer. 1998;82(11):2256–61.CrossRefPubMedGoogle Scholar
  22. 22.
    Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3(1):81–5.PubMedGoogle Scholar
  23. 23.
    Afshar-Oromieh A, Haberkorn U, Eder M, Eisenhut M, Zechmann CM. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH. Eur J Nucl Med Mol Imaging. 2012;39(6):1085–6. doi: 10.1007/s00259-012-2069-0.CrossRefPubMedGoogle Scholar
  24. 24.
    Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. 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. doi: 10.2967/jnumed.115.160382.CrossRefPubMedGoogle Scholar
  25. 25.
    Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, 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(1):11–20. doi: 10.1007/s00259-013-2525-5.CrossRefPubMedGoogle Scholar
  26. 26.
    Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of (68)gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195(5):1436–43. doi: 10.1016/j.juro.2015.12.025.CrossRefPubMedGoogle Scholar
  27. 27.
    Budäus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, et al. Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol. 2016;69(3):393–6. doi: 10.1016/j.eururo.2015.06.010.CrossRefPubMedGoogle Scholar
  28. 28.
    World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2000;284:3043–5.Google Scholar
  29. 29.
    Mueller D, Klette I, Baum RP, Gottschaldt M, Schultz MK, Breeman WA. Simplified NaCl based (68)Ga concentration and labeling procedure for rapid synthesis of (68)Ga radiopharmaceuticals in high radiochemical purity. Bioconjug Chem. 2012;23(8):1712–7. doi: 10.1021/bc300103t.CrossRefPubMedGoogle Scholar
  30. 30.
    Eder M, Neels O, Müller M, Bauder-Wüst U, Remde Y, Schäfer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals (Basel). 2014;7(7):779–96.CrossRefGoogle Scholar
  31. 31.
    Rauscher I, Maurer T, Fendler WP, Sommer WH, Schwaiger M, Eiber M. (68)Ga-PSMA ligand PET/CT in patients with prostate cancer: how we review and report. Cancer Imaging. 2016;16(1):14. doi: 10.1186/s40644-016-0072-6. Review.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Schäfer M, Bauder-Wüst U, Leotta K, Zoller F, Mier W, Haberkorn U, et al. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res. 2012;2(1):23. doi: 10.1186/2191-219X-2-23.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Eder M, Schäfer M, Bauder-Wüst U, Hull WE, Wängler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. EJNMMI Res. 2012;2(1):23. doi: 10.1186/2191-219X-2-23.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Demirci E, Sahin OE, Ocak M, Akovali B, Nematyazar J, Kabasakal L. Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging. Nucl Med Commun. 2016;37(11):1169–79. doi: 10.1097/MNM.0000000000000566.CrossRefPubMedGoogle Scholar
  35. 35.
    Sachpekidis C, Kopka K, Eder M, Hadaschik BA, Freitag MT, Pan L, et al. 68Ga-PSMA-11 dynamic PET/CT imaging in primary prostate cancer. Clin Nucl Med. 2016;41(11):e473–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, et al. 68Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol. 2016. doi: 10.1016/j.eururo.2015.12.051.PubMedGoogle Scholar
  37. 37.
    Kabasakal L, Demirci E, Ocak M, Akyel R, Nematyazar J, Aygun A, 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. 2015;36(6):582–7. doi: 10.1097/MNM.0000000000000290.CrossRefPubMedGoogle Scholar
  38. 38.
    Sahlmann CO, Meller B, Bouter C, Ritter CO, Ströbel P, Lotz J, et al. Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma. Eur J Nucl Med Mol Imaging. 2016;43(5):898–905. doi: 10.1007/s00259-015-3251-y.CrossRefPubMedGoogle Scholar
  39. 39.
    Schwenck J, Rempp H, Reischl G, Kruck S, Stenzl A, Nikolaou K, et al. Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging. 2016.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Christian Uprimny
    • 1
  • Alexander Stephan Kroiss
    • 1
  • Clemens Decristoforo
    • 1
  • Josef Fritz
    • 2
  • Elisabeth von Guggenberg
    • 1
  • Dorota Kendler
    • 1
  • Lorenza Scarpa
    • 1
  • Gianpaolo di Santo
    • 1
  • Llanos Geraldo Roig
    • 1
  • Johanna Maffey-Steffan
    • 1
  • Wolfgang Horninger
    • 3
  • Irene Johanna Virgolini
    • 1
  1. 1.Department of Nuclear MedicineMedical University InnsbruckInnsbruckAustria
  2. 2.Department of Medical Statistics, Informatics and Health EconomicsMedical University InnsbruckInnsbruckAustria
  3. 3.Department of UrologyMedical University InnsbruckInnsbruckAustria

Personalised recommendations