Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2018

01-10-2018 | Original Article

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

Authors: Christian Uprimny, Anna Svirydenka, Josef Fritz, Alexander Stephan Kroiss, Bernhard Nilica, Clemens Decristoforo, Roland Haubner, Elisabeth von Guggenberg, Sabine Buxbaum, Wolfgang Horninger, Irene Johanna Virgolini

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2018

Login to get access

Abstract

Aim

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.

Methods

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.

Results

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).

Conclusion

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.
Appendix
Available only for authorised users
Literature
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.CrossRefPubMed
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.
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.CrossRefPubMed
4.
Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27(3):165–76.CrossRefPubMed
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.CrossRefPubMed
6.
Saad F, Clarke N, Colombel M. Natural history and treatment of bone complications in prostate cancer. Eur Urol. 2006;49(3):429–40.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.
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.
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.
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.PubMed
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.CrossRefPubMed
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.PubMed
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.PubMed
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.
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
23.
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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):941-949CrossRefPubMed
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. https://​doi.​org/​10.​1007/​s00330-017-4994-6.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
35.
Durkalski VL, Palesch YY, Lipsitz SR, Rust PF. Analysis of clustered matched-pair data. Stat Med. 2003;22(15):2417–28.CrossRefPubMed
36.
Rosner B, Glynn RJ, Lee ML. The Wilcoxon signed rank test for paired comparisons of clustered data. Biometrics. 2006;62(1):185–92.CrossRefPubMed
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.CrossRefPubMed
38.
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
44.
45.
Keller ET, Brown J. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biochem. 2004;91(4):718–29. ReviewCrossRefPubMed
46.
Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007 Jun;48(6):932–45.CrossRefPubMed
47.
Moses WW. Fundamental Limits of spatial resolution in PET. Nucl Instrum Methods Phys Res A. 2011;648(Supplement 1):S236–40.
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.CrossRefPubMed
49.
van Schelven WD, Pauwels EK. The flare phenomenon: far from fair and square. Eur J Nucl Med. 1994;21(5):377–80.CrossRefPubMed
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.CrossRefPubMed
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.PubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
55.
World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2000;284:3043–5.CrossRef
Metadata
Title
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
Authors
Christian Uprimny
Anna Svirydenka
Josef Fritz
Alexander Stephan Kroiss
Bernhard Nilica
Clemens Decristoforo
Roland Haubner
Elisabeth von Guggenberg
Sabine Buxbaum
Wolfgang Horninger
Irene Johanna Virgolini
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-4048-6

Other articles of this Issue 11/2018

European Journal of Nuclear Medicine and Molecular Imaging 11/2018 Go to the issue

Original Article

Prognostic value of myocardial perfusion imaging performed pre-renal transplantation: post-transplantation follow-up and outcomes

Original Article

Trifunctional PSMA-targeting constructs for prostate cancer with unprecedented localization to LNCaP tumors

Original Article

Risk-related 18F-FDG PET/CT and new diagnostic strategies in patients with solitary pulmonary nodule: the ITALIAN multicenter trial

Original Article

68Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients

Image of the Month

A rare presentation of skull-base osteomyelitis with neurovascular sheath extension following external otitis resolved by PET/MRI

Book Review

Ferdinando Calabria and Orazio Schillaci (Eds). Radiopharmaceuticals. Metabolic Pathways for PET/CT and PET/MRI Imaging