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Prospective comparison of 68Ga-PSMA PET/CT, 18F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer

  • Helle D. Zacho
  • Julie B. Nielsen
  • Ali Afshar-Oromieh
  • Uwe Haberkorn
  • Nandita deSouza
  • Katja De Paepe
  • Katja Dettmann
  • Niels C. Langkilde
  • Christian Haarmark
  • Rune V. Fisker
  • Dennis T. Arp
  • Jesper Carl
  • Jørgen B. Jensen
  • Lars J. Petersen
Original Article

Abstract

Purpose

To prospectively compare diagnostic accuracies for detection of bone metastases by 68Ga-PSMA PET/CT, 18F-NaF PET/CT and diffusion-weighted MRI (DW600-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR).

Methods

Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68Ga-PSMA PET/CT, a 18F-NaF PET/CT and a DW600-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm2). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic.

Results

Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98–1.00 and 0.89–0.90 for 68Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90–0.98 and 0.90–0.94 for 18NaF PET/CT (n = 67 patients); and 0.25–0.38, 0.87–0.92 and 0.59–0.62 for DW600-MRI (n = 60 patients). The diagnostic performance of DW600-MRI was significantly lower than that of 68Ga-PSMA PET/CT and 18NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68Ga-PSMA PET/CT and 18NaF PET/CT (p = 0.65).

Conclusion

68Ga-PSMA PET/CT and 18F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW600-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

Keywords

PSMA-PET/CT NaF-PET/CT Diffusion-weighted MRI Bone metastases Prostate cancer 

Notes

Funding

This study was supported by unrestricted grants from the Obel Family Foundation and the Danielsen foundation.

Compliance with ethical standards

Conflict of interest

HDZ received grant funding from the Danielsen Foundation, NdS receives grant funding from Cancer Research UK, KDP is a Cancer Research UK funded fellow and LJP receives grant foundation form the Obel Family Foundation. The authors have no other conflicts of interest regarding the present manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Supplementary material

259_2018_4058_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 14 kb)

References

  1. 1.
    Suardi N, Porter CR, Reuther AM, Walz J, Kodama K, Gibbons RP, et al. A nomogram predicting long-term biochemical recurrence after radical prostatectomy. Cancer. 2008;112:1254–63.  https://doi.org/10.1002/cncr.23293.CrossRefPubMedGoogle Scholar
  2. 2.
    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;71:630–42.  https://doi.org/10.1016/j.eururo.2016.08.002.CrossRefPubMedGoogle Scholar
  3. 3.
    Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65:467–79.CrossRefPubMedGoogle Scholar
  4. 4.
    Schweizer MT, Zhou XC, Wang H, Yang T, Shaukat F, Partin AW, et al. Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy. Ann Oncol. 2013;24:2881–6.  https://doi.org/10.1093/annonc/mdt335.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Norgaard M, Jensen AO, Jacobsen JB, Cetin K, Fryzek JP, Sorensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007). J Urol. 2010;184:162–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of (68)Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44:1258–68.  https://doi.org/10.1007/s00259-017-3711-7.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid (6)(8)Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74.  https://doi.org/10.2967/jnumed.115.154153.CrossRefPubMedGoogle Scholar
  8. 8.
    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;42:197–209.  https://doi.org/10.1007/s00259-014-2949-6.CrossRefPubMedGoogle Scholar
  9. 9.
    Calais J, Czernin J, Cao M, Kishan AU, Hegde JV, Shaverdian N, et al. (68)Ga-PSMA PET/CT mapping of prostate cancer biochemical recurrence following radical prostatectomy in 270 patients with PSA<1.0ng/ml: impact on salvage radiotherapy planning. J Nucl Med. 2017;  https://doi.org/10.2967/jnumed.117.201749.
  10. 10.
    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;  https://doi.org/10.1007/s00259-016-3435-0.
  11. 11.
    Lofgren J, Mortensen J, Rasmussen SH, Madsen C, Loft A, Hansen AE, et al. A prospective study comparing 99mTc-HDP planar bone scintigraphy and whole-body SPECT/CT with 18F-fluoride PET/CT and 18F-fluoride PET/MRI for diagnosing bone metastases. J Nucl Med. 2017;  https://doi.org/10.2967/jnumed.116.189183.
  12. 12.
    Padhani AR, Lecouvet FE, Tunariu N, Koh DM, De Keyzer F, Collins DJ, et al. Rationale for modernising imaging in advanced prostate cancer. European Urology Focus. 2017;3:223–39.  https://doi.org/10.1016/j.euf.2016.06.018.CrossRefPubMedGoogle Scholar
  13. 13.
    Lecouvet FE, El MJ, Collette L, Coche E, Danse E, Jamar F, 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. 2012;62:68–75.CrossRefPubMedGoogle Scholar
  14. 14.
    Mosavi F, Johansson S, Sandberg DT, Turesson I, Sorensen J, Ahlstrom H. Whole-body diffusion-weighted MRI compared with (18)F-NaF PET/CT for detection of bone metastases in patients with high-risk prostate carcinoma. AJR Am J Roentgenol. 2012;199:1114–20.  https://doi.org/10.2214/ajr.11.8351.CrossRefPubMedGoogle Scholar
  15. 15.
    Eiber M, Holzapfel K, Ganter C, Epple K, Metz S, Geinitz H, et al. Whole-body MRI including diffusion-weighted imaging (DWI) for patients with recurring prostate cancer: technical feasibility and assessment of lesion conspicuity in DWI. Journal of Magnetic Resonance Imaging : JMRI. 2011;33:1160–70.  https://doi.org/10.1002/jmri.22542.CrossRefPubMedGoogle Scholar
  16. 16.
    Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, et al. ESUR prostate MR guidelines 2012. Eur Radiol. 2012;22:746–57.  https://doi.org/10.1007/s00330-011-2377-y.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Larbi A, Dallaudiere B, Pasoglou V, Padhani A, Michoux N, Vande Berg BC, et al. Whole body MRI (WB-MRI) assessment of metastatic spread in prostate cancer: therapeutic perspectives on targeted management of oligometastatic disease. Prostate. 2016;76:1024–33.  https://doi.org/10.1002/pros.23196.CrossRefPubMedGoogle Scholar
  18. 18.
    Lecouvet FE, Talbot JN, Messiou C, Bourguet P, Liu Y, de Souza NM. Monitoring the response of bone metastases to treatment with magnetic resonance imaging and nuclear medicine techniques: a review and position statement by the European Organisation for Research and Treatment of Cancer imaging group. European Journal of Cancer (Oxford, England : 1990). 2014;50:2519–31.  https://doi.org/10.1016/j.ejca.2014.07.002.CrossRefGoogle Scholar
  19. 19.
    Nielsen JB, Zacho HD, Haberkorn U, Nielsen KM, Dettmann K, Langkilde NC, et al. A comprehensive safety evaluation of 68Ga-labeled ligand prostate-specific membrane antigen 11 PET/CT in prostate cancer: the results of 2 prospective, multicenter trials. Clin Nucl Med. 2017;42:520–4.  https://doi.org/10.1097/rlu.0000000000001681.CrossRefPubMedGoogle Scholar
  20. 20.
    Zacho HD, Nielsen JB, Haberkorn U, Nielsen KM, Dettmann K, Langkilde NC, et al. 68Ga-PSMA PET/CT in patients with biochemical recurrence of prostate cancer: a prospective, two-center study. Clin Nucl Med. 2018.Google Scholar
  21. 21.
    Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. 68Ga-PSMA PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017;44:1014–24.  https://doi.org/10.1007/s00259-017-3670-z.CrossRefPubMedGoogle Scholar
  22. 22.
    Segall G, Delbeke D, Stabin MG, Even-Sapir E, Fair J, Sajdak R, et al. SNM practice guideline for sodium 18F-fluoride PET/CT bone scans 1.0. J Nucl Med. 2010;51:1813–20.CrossRefPubMedGoogle Scholar
  23. 23.
    Fendler WP, Calais J, Allen-Auerbach M, Bluemel C, Eberhardt N, Emmett L, et al. 68Ga-PSMA-11 PET/CT interobserver agreement for prostate cancer assessments: an international multicenter prospective study. J Nucl Med. 2017;  https://doi.org/10.2967/jnumed.117.190827.
  24. 24.
    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: the Official Publication of the International Cancer Imaging Society. 2016;16:14.  https://doi.org/10.1186/s40644-016-0072-6. CrossRefGoogle Scholar
  25. 25.
    Fonager RF, Zacho HD, Langkilde NC, Fledelius J, Ejlersen JA, Haarmark C, et al. Diagnostic test accuracy study of (18)F-sodium fluoride PET/CT, (99m)Tc-labelled diphosphonate SPECT/CT, and planar bone scintigraphy for diagnosis of bone metastases in newly diagnosed, high-risk prostate cancer. American Journal of Nuclear Medicine and Molecular Imaging. 2017;7:218–27.PubMedPubMedCentralGoogle Scholar
  26. 26.
    DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.CrossRefPubMedGoogle Scholar
  27. 27.
    Zacho HD, Nielsen JB, Haberkorn U, Stenholt L, Petersen LJ. (68) Ga-PSMA PET/CT for the detection of bone metastases in prostate cancer: a systematic review of the published literature. Clin Physiol Funct Imaging. 2017;  https://doi.org/10.1111/cpf.12480.
  28. 28.
    Akamatsu G, Ishikawa K, Mitsumoto K, Taniguchi T, Ohya N, Baba S, et al. Improvement in PET/CT image quality with a combination of point-spread function and time-of-flight in relation to reconstruction parameters. J Nucl Med. 2012;53:1716–22.  https://doi.org/10.2967/jnumed.112.103861.CrossRefPubMedGoogle Scholar
  29. 29.
    Poulsen MH, Petersen H, Hoilund-Carlsen PF, Jakobsen JS, Gerke O, Karstoft J, et al. Spine metastases in prostate cancer: comparison of [ Tc]MDP wholebody bone scintigraphy, [ F]choline PET/CT, and [ F]NaF PET/CT. BJU Int. 2014;114(6):818–23.  https://doi.org/10.1111/bju.12599.CrossRefPubMedGoogle Scholar
  30. 30.
    Wondergem M, van der Zant FM, van der Ploeg T, Knol RJJ. A literature review of 18 F-fluoride PET/CT and 18 F-choline or 11 C-choline PET/CT for detection of bonemtastases in patients with prostate cancer. Nucl Med Commun. 2013;34:935–45.CrossRefPubMedGoogle Scholar
  31. 31.
    Damle NA, Bal C, Bandopadhyaya GP, Kumar L, Kumar P, Malhotra A, et al. The role of 18F-fluoride PET-CT in the detection of bone metastases in patients with breast, lung and prostate carcinoma: a comparison with FDG PET/CT and 99mTc-MDP bone scan. Jpn J Radiol. 2013;31:262–9.  https://doi.org/10.1007/s11604-013-0179-7.CrossRefPubMedGoogle Scholar
  32. 32.
    Iagaru AH, Mittra E, Colletti PM, Jadvar H. Bone-targeted imaging and radionuclide therapy in prostate cancer. J Nucl Med. 2016;57:19s–24s.  https://doi.org/10.2967/jnumed.115.170746.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Gutzeit A, Doert A, Froehlich JM, Eckhardt BP, Meili A, Scherr P, et al. Comparison of diffusion-weighted whole body MRI and skeletal scintigraphy for the detection of bone metastases in patients with prostate or breast carcinoma. Skelet Radiol. 2010;39:333–43.CrossRefGoogle Scholar
  34. 34.
    Nakanishi K, Kobayashi M, Nakaguchi K, Kyakuno M, Hashimoto N, Onishi H, et al. Whole-body MRI for detecting metastatic bone tumor: diagnostic value of diffusion-weighted images. Magnetic Resonance in Medical Sciences : MRMS : an Official Journal of Japan Society of Magnetic Resonance in Medicine. 2007;6:147–55.CrossRefGoogle Scholar
  35. 35.
    Padhani AR, Lecouvet FE, Tunariu N, Koh DM, De Keyzer F, Collins DJ, et al. METastasis reporting and data system for prostate cancer: practical guidelines for acquisition, interpretation, and reporting of whole-body magnetic resonance imaging-based evaluations of multiorgan involvement in advanced prostate cancer. Eur Urol. 2017;71:81–92.  https://doi.org/10.1016/j.eururo.2016.05.033.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    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;39:1085–6.CrossRefPubMedGoogle Scholar
  37. 37.
    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;40:486–95.  https://doi.org/10.1007/s00259-012-2298-2.CrossRefPubMedGoogle Scholar
  38. 38.
    Verburg FA, Pfister D, Heidenreich A, Vogg A, Drude NI, Voo S, et al. Extent of disease in recurrent prostate cancer determined by [(68)Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score. Eur J Nucl Med Mol Imaging. 2016;43:397–403.  https://doi.org/10.1007/s00259-015-3240-1.CrossRefPubMedGoogle Scholar
  39. 39.
    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;41:11–20.  https://doi.org/10.1007/s00259-013-2525-5.CrossRefPubMedGoogle Scholar
  40. 40.
    Fonager RF, Zacho HD, Langkilde NC, Fledelius J, Ejlersen JA, Hendel HW, et al. Prospective comparative study of (18)F-sodium fluoride PET/CT and planar bone scintigraphy for treatment response assessment of bone metastases in patients with prostate cancer. Acta Oncol. 2018:1–7.  https://doi.org/10.1080/0284186x.2018.1438651.

Copyright information

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

Authors and Affiliations

  • Helle D. Zacho
    • 1
    • 2
  • Julie B. Nielsen
    • 1
    • 2
  • Ali Afshar-Oromieh
    • 3
    • 4
  • Uwe Haberkorn
    • 3
    • 5
  • Nandita deSouza
    • 6
  • Katja De Paepe
    • 6
  • Katja Dettmann
    • 7
  • Niels C. Langkilde
    • 8
  • Christian Haarmark
    • 9
  • Rune V. Fisker
    • 1
    • 10
  • Dennis T. Arp
    • 11
  • Jesper Carl
    • 12
  • Jørgen B. Jensen
    • 7
    • 13
  • Lars J. Petersen
    • 1
    • 2
  1. 1.Department of Nuclear Medicine and Clinical Cancer Research CenterAalborg University HospitalAalborgDenmark
  2. 2.Department of Clinical MedicineAalborg UniversityAalborgDenmark
  3. 3.Department of Nuclear MedicineUniversity Hospital HeidelbergHeidelbergGermany
  4. 4.Department of Nuclear MedicineBern University HospitalBernSwitzerland
  5. 5.Clinical Cooperation Unit Nuclear MedicineDKFZHeidelbergGermany
  6. 6.The Institute of Cancer Research and Royal Marsden NHS Foundation TrustLondonUK
  7. 7.Department of UrologyRegional Hospital West JutlandHolstebroDenmark
  8. 8.Department of UrologyAalborg University HospitalAalborgDenmark
  9. 9.Department of Clinical Physiology and Nuclear MedicineHerlev and Gentofte HospitalHerlevDenmark
  10. 10.Department of RadiologyAalborg University HospitalAalborgDenmark
  11. 11.Department of Medical Physics, Oncology DepartmentAalborg University HospitalAalborgDenmark
  12. 12.Department of Oncology, Naestved SygehusZealand University HospitalRoskildeDenmark
  13. 13.Department of Clinical MedicineAarhus UniversityAarhusDenmark

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