Comparison of [68Ga]Ga-PSMA-11 PET/CT with [18F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy

  • Christian UprimnyEmail author
  • Anna Svirydenka
  • Josef Fritz
  • Alexander Stephan Kroiss
  • Bernhard Nilica
  • Clemens Decristoforo
  • Roland Haubner
  • Elisabeth von Guggenberg
  • Sabine Buxbaum
  • Wolfgang Horninger
  • Irene Johanna Virgolini
Original Article



The purpose of this study was to investigate the diagnostic performance of 68Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [18F]sodium fluoride (18F-NaF) PET/CT.


Sixteen metastatic PC patients with known skeletal metastases, who underwent both 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on 18F-NaF PET and 68Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUVmax) and compared to background activity of normal bone. In addition, SUVmax values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan.


In contrast to 468 PET-positive lesions suggestive of bone metastases on 18F-NaF PET, only 351 of the lesions were also judged positive on 68Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on 18F-NaF PET compared to 68Ga-PSMA-11 PET, showing a median SUVmax of 27.0 and 6.0, respectively (p < 0.001). Background activity of normal bone was lower on 68Ga-PSMA-11 PET, with a median SUVmax of 1.0 in comparison to 2.7 on 18F-NaF PET; however, tumour to background ratio was significantly higher on 18F-NaF PET (9.8 versus 5.9 on 68Ga-PSMA-11 PET; p = 0.042). Based on morphologic lesion characterisation on CT, 18F-NaF PET revealed median SUVmax values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on 68Ga-PSMA-11 PET median SUVmax values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between18F-NaF PET and 68Ga-PSMA-11 PET was significantly higher in osteosclerotic (p < 0.001) and lesions not visible on CT (p = 0.012).


In comparison to 68Ga-PSMA-11 PET/CT, 18F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that 68Ga-PSMA-11 PET should be combined with 18F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.


Prostate cancer Bone metastases Restaging 68Ga-PSMA-11 PET/CT 18F-NaF PET/CT 



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 subsequent amendments [55]. All patients published in this manuscript signed a written informed consent to the PET studies.

Supplementary material

259_2018_4048_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 16 kb)


  1. 1.
    Arnold M, Karim-Kos HE, Coebergh JW, Byrnes G, Antilla A, Ferlay J, et al. Recent trends in incidence of five common cancers in 26 European countries since 1988: Analysis of the European Cancer Observatory. Recent trends in incidence of five common cancers in 26 European countries since 1988: Analysis of the European Cancer Observatory. Eur J Cancer. 2015;51(9):1164–87.CrossRefPubMedGoogle Scholar
  2. 2.
    Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61(6):1079–92.Google Scholar
  3. 3.
    Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31(5):578–83.CrossRefPubMedGoogle Scholar
  4. 4.
    Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27(3):165–76.CrossRefPubMedGoogle Scholar
  5. 5.
    Nørgaard M, Jensen AØ, Jacobsen JB, Cetin K, Fryzek JP, Sørensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007). J Urol. 2010;184(1):162–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Saad F, Clarke N, Colombel M. Natural history and treatment of bone complications in prostate cancer. Eur Urol. 2006;49(3):429–40.CrossRefPubMedGoogle Scholar
  7. 7.
    Tait C, Moore D, Hodgson C, Brown M, Morris T, Growcott J, et al. Quantification of skeletal metastases in castrate-resistant prostate cancer predicts progression-free and overall survival. BJU Int. 2014;114(6b):E70–3.CrossRefPubMedGoogle Scholar
  8. 8.
    Handkiewicz-Junak D, Poeppel TD, Bodei L, Aktolun C, Ezziddin S, Giammarile F, et al. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides. Eur J Nucl Med Mol Imaging. 2018;45(5):846–59.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG Guidelines on prostate cancer. part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017;71(4):630–42.CrossRefPubMedGoogle Scholar
  10. 10.
    Virgolini I, Decristoforo C, Haug A, Fanti S, Uprimny C. Current status of theranostics in prostate cancer. Eur J Nucl Med Mol Imaging. 2017.Google Scholar
  11. 11.
    von Eyben FE, Roviello G, Kiljunen T, Uprimny C, Virgolini I, Kairemo K, et al. Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review. Eur J Nucl Med Mol Imaging. 2017.Google Scholar
  12. 12.
    Poeppel TD, Handkiewicz-Junak D, Andreeff M, Becherer A, Bockisch A, Fricke E, et al. EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017.Google Scholar
  13. 13.
    Evangelista L, Bertoldo F, Boccardo F, Conti G, Menchi I, Mungai F, et al. Diagnostic imaging to detect and evaluate response to therapy in bone metastases from prostate cancer: current modalities and new horizons. Eur J Nucl Med Mol Imaging. 2016;43:1546–62.CrossRefPubMedGoogle Scholar
  14. 14.
    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. 2017;71(4):618–29.CrossRefPubMedGoogle Scholar
  15. 15.
    Beheshti M, Rezaee A, Geinitz H, Loidl W, Pirich C, Langsteger W. Evaluation of prostate cancer bone metastases with 18F-NaF and 18F-Fluorocholine PET/CT. J Nucl Med. 2016;57:55S–60S.CrossRefPubMedGoogle Scholar
  16. 16.
    Cook GJ, Azad G, Padhani AR. Bone imaging in prostate cancer: the evolving roles of nuclear medicine and radiology. Can J Urol. 2016;23(6):8564–7.PubMedGoogle Scholar
  17. 17.
    Langsteger W, Rezaee A, Pirich C, Beheshti M. 18F-NaF-PET/CT and 99mTc-MDP bone scintigraphy in the detection of bone metastases in prostate cancer. Semin Nucl Med. 2016;46(6):491–501.CrossRefPubMedGoogle Scholar
  18. 18.
    Schirrmeister H, Glatting G, Hetzel J, Nüssle K, Arslandemir C, Buck AK, et al. Prospective evaluation of the clinical value of planar bone scans, SPECT, and (18)F-labeled NaF PET in newly diagnosed lung cancer. J Nucl Med. 2001;42(12):1800–4.PubMedGoogle Scholar
  19. 19.
    Schirrmeister H, Guhlmann A, Elsner K, Kotzerke J, Glatting G, Rentschler M, et al. Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET. J Nucl Med. 1999;40(10):1623–9.PubMedGoogle Scholar
  20. 20.
    Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Hammer J, et al. The use of F-18 choline PET in the assessment of bone metastases in prostate cancer: correlation with morphological changes on CT. Mol Imaging Biol. 2010;12(1):98–107.Google Scholar
  21. 21.
    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(6):971–2.CrossRefPubMedGoogle Scholar
  22. 22.
    Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44(8):1258–68.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Schwarzenbock SM, Rauscher I, Bluemel C, Fendler WP, Rowe SP, Pomper MG, et al. PSMA ligands for PET-imaging of prostate cancer. J Nucl Med. 2017;58(10):1545–1552
  24. 24.
    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 2017;44(1):92–101.CrossRefPubMedGoogle Scholar
  25. 25.
    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.CrossRefPubMedGoogle Scholar
  26. 26.
    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.CrossRefPubMedGoogle Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    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.CrossRefPubMedGoogle Scholar
  29. 29.
    Uprimny C, Kroiss AS, Decristoforo C, Fritz J, von Guggenberg E, Kendler D, et al. 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. Eur J Nucl Med Mol Imaging. 2017;44(6):941-949CrossRefPubMedGoogle Scholar
  30. 30.
    Janssen JC, Meißner S, Woythal N, Prasad V, Brenner W, Diederichs G, et al. Comparison of hybrid 68Ga-PSMA-PET/CT and 99mTc-DPD-SPECT/CT for the detection of bone metastases in prostate cancer patients: additional value of morphologic information from low dose CT. Eur Radiol. 2018;28(2):610-619. Scholar
  31. 31.
    Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016 Nov;43(12):2114–21.CrossRefPubMedGoogle Scholar
  32. 32.
    Uprimny C, Kroiss A, Nilica B, Buxbaum S, Decristoforo C, Horninger W, et al. (68)Ga-PSMA ligand PET versus (18)F-NaF PET: evaluation of response to (223)Ra therapy in a prostate cancer patient. Eur J Nucl Med Mol Imaging. 2015;42(2):362–3.CrossRefPubMedGoogle Scholar
  33. 33.
    Uprimny C, Kroiss AS, Decristoforo C, Fritz J, Warwitz B, Scarpa L, et al. Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions. Eur J Nucl Med Mol Imaging. 2017;44(5):765–75.CrossRefPubMedGoogle Scholar
  34. 34.
    Segall G, Delbeke D, Stabin MG, Even-Sapir E, Fair J, Sajdak R, et al. SNM. SNM practice guideline for sodium 18F-fluoride PET/CT bone scans 1.0. J Nucl Med. 2010;51(11):1813–20.CrossRefPubMedGoogle Scholar
  35. 35.
    Durkalski VL, Palesch YY, Lipsitz SR, Rust PF. Analysis of clustered matched-pair data. Stat Med. 2003;22(15):2417–28.CrossRefPubMedGoogle Scholar
  36. 36.
    Rosner B, Glynn RJ, Lee ML. The Wilcoxon signed rank test for paired comparisons of clustered data. Biometrics. 2006;62(1):185–92.CrossRefPubMedGoogle Scholar
  37. 37.
    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;70(6):926–37.CrossRefPubMedGoogle Scholar
  38. 38.
    Araz M, Aras G, Küçük ÖN. The role of 18F-NaF PET/CT in metastatic bone disease. J Bone Oncol. 2015;4(3):92–7.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Even-Sapir E, Mishani E, Flusser G, Metser U. 18F-fluoride positron emission tomography and positron emission tomography/computed tomography. Semin Nucl Med. 2007 Nov;37(6):462–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Etchebehere EC, Araujo JC, Fox PS, Swanston NM, Macapinlac HA, Rohren EM. Prognostic factors in patients treated with 223Ra: the role of skeletal tumor burden on baseline 18F-fluoride PET/CT in predicting overall survival. J Nucl Med. 2015;56(8):1177–84.CrossRefPubMedGoogle Scholar
  41. 41.
    Ibrahim T, Flamini E, Mercatali L, Sacanna E, Serra P, Amadori D. Pathogenesis of osteoblastic bone metastases from prostate cancer. Cancer. 2010;116(6):1406–18.CrossRefPubMedGoogle Scholar
  42. 42.
    Janssen JC, Woythal N, Meißner S, Prasad V, Brenner W, Diederichs G, et al. [68Ga]PSMA-HBED-CC uptake in osteolytic, osteoblastic, and bone marrow metastases of prostate cancer patients. Mol Imaging Biol. 2017;19(6):933–43.CrossRefPubMedGoogle Scholar
  43. 43.
    Yang HL, Liu T, Wang XM, Xu Y, Deng SM. Diagnosis of bone metastases: a meta-analysis comparing 18FDG PET, CT, MRI and bone scintigraphy. Eur Radiol. 2011;21(12):2604–17.CrossRefPubMedGoogle Scholar
  44. 44.
    Jin JK, Dayyani F, Gallick GE. Steps in prostate cancer progression that lead to bone metastasis. Int J Cancer. 2011;128(11):2545–61.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Keller ET, Brown J. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biochem. 2004;91(4):718–29. ReviewCrossRefPubMedGoogle Scholar
  46. 46.
    Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007 Jun;48(6):932–45.CrossRefPubMedGoogle Scholar
  47. 47.
    Moses WW. Fundamental Limits of spatial resolution in PET. Nucl Instrum Methods Phys Res A. 2011;648(Supplement 1):S236–40.Google Scholar
  48. 48.
    Sánchez-Crespo A, Andreo P, Larsson SA. Positron flight in human tissues and its influence on PET image spatial resolution. Eur J Nucl Med Mol Imaging. 2004;31(1):44–51.CrossRefPubMedGoogle Scholar
  49. 49.
    van Schelven WD, Pauwels EK. The flare phenomenon: far from fair and square. Eur J Nucl Med. 1994;21(5):377–80.CrossRefPubMedGoogle Scholar
  50. 50.
    Rossleigh MA, Lovegrove FT, Reynolds PM, Byrne MJ. Serial bone scans in the assessment of response to therapy in advanced breast carcinoma. Clin Nucl Med. 1982;7(9):397–402.CrossRefPubMedGoogle Scholar
  51. 51.
    Coleman RE, Mashiter G, Whitaker KB, Moss DW, Rubens RD, Fogelman I. Bone scan flare predicts successful systemic therapy for bone metastases. J Nucl Med. 1988;29(8):1354–9.PubMedGoogle Scholar
  52. 52.
    Pollen JJ, Witztum KF, Ashburn WL. The flare phenomenon on radionuclide bone scan in metastatic prostate cancer. AJR Am J Roentgenol. 1984;142(4):773–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Sundkvist GM, Ahlgren L, Lilja B, Mattsson S, Abrahamsson PA, Wadström LB. Repeated quantitative bone scintigraphy in patients with prostatic carcinoma treated with orchiectomy. Eur J Nucl Med. 1988;14(4):203–6.CrossRefPubMedGoogle Scholar
  54. 54.
    Sundkvist GM, Björk T, Kjellström H, Lilja B. Quantitative bone scintigraphy in patients with prostatic carcinoma treated with LH-RH analogues. Scand J Urol Nephrol. 1996;30(1):29–32.CrossRefPubMedGoogle Scholar
  55. 55.
    World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2000;284:3043–5.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Christian Uprimny
    • 1
    Email author
  • Anna Svirydenka
    • 1
  • Josef Fritz
    • 2
  • Alexander Stephan Kroiss
    • 1
  • Bernhard Nilica
    • 1
  • Clemens Decristoforo
    • 1
  • Roland Haubner
    • 1
  • Elisabeth von Guggenberg
    • 1
  • Sabine Buxbaum
    • 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