Skip to main content

Clinical insignificance of [18F]PSMA-1007 avid non-specific bone lesions: a retrospective evaluation

Abstract

Purpose

[18F]PSMA-1007 offers advantages of low urinary tracer excretion and theoretical improved spatial resolution for imaging prostate cancer. However, non-specific bone lesions (NSBLs), defined as mild to moderate focal bone uptake without a typical morphological correlate on CT, are a common finding on [18F]PSMA-1007 PET/CT. The purpose of this study was to investigate the clinical outcomes of patients with [18F]PSMA-1007 avid NSBLs, to determine whether patients with NSBLs represent a higher risk clinical cohort, and to determine whether SUVmax can be used as a classifier of bone metastasis.

Methods

A retrospective audit of 214 men with prostate cancer was performed to investigate the clinical outcomes of [18F]PSMA-1007 avid NSBLs according to defined criteria. We also compared the serum PSA, Gleason score, and uptake time of patients with [18F]PSMA-1007 avid NSBLs to patients without [18F]PSMA-1007 avid bone lesions. Finally, we analysed an SUVmax threshold to identify bone metastases using ROC curve analysis.

Results

Ninety-four of 214 patients (43.9%) demonstrated at least one NSBL. No [18F]PSMA-1007 avid NSBLs met criteria for a likely malignant or definitely malignant lesion after a median 15.8-month follow-up interval (11.9% definitely benign, 50.3% likely benign, and 37.7% equivocal). There were no statistically significant differences in serum PSA, Gleason score, and uptake time between patients with [18F]PSMA-1007 avid NSBLs and those without [18F]PSMA-1007 avid bone lesions. All NSBLs with adequate follow-up had SUVmax ≤ 11.1. The value of the highest SUVmax distinguished between NSBLs and definite prostate cancer bone metastases, whereby an SUVmax threshold of ≥ 7.2 maximized the Youden’s index.

Conclusion

[18F]PSMA-1007 avid NSBLs rarely represent prostate cancer bone metastases. When identified in the absence of definite metastatic disease elsewhere, it is appropriate to classify those with SUVmax < 7.2 as likely benign. NSBLs with SUVmax 7.2–11.1 may be classified as equivocal or metastatic, with patient clinical risk factors, scan appearance, and potential management implications used to guide interpretation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Data availability

Not applicable.

Code availability

Not applicable.

References

  1. Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. The Lancet. 2020;395:1208–16. https://doi.org/10.1016/S0140-6736(20)30314-7.

    CAS  Article  Google Scholar 

  2. Kesch C, Kratochwil C, Mier W, Kopa K and Giesel FL. Gallium-68 or fluorine-18 for prostate cancer imaging? J Nucl Med. 2017:687-8.

  3. Dietlein F, Kobe C, Hohberg M, Zlatopolskiy BD, Krapf P, Endepols H, et al. Intraindividual comparison of 18 F-PSMA-1007 with renally excreted PSMA ligands for PSMA PET imaging in patients with relapsed prostate cancer. J Nucl Med. 2020;61:729.

    CAS  Article  Google Scholar 

  4. Derlin T, Weiberg D, von Klot C, Wester HJ, Henkenberens C, Ross TL, et al. (68)Ga-PSMA I&T PET/CT for assessment of prostate cancer: evaluation of image quality after forced diuresis and delayed imaging. Eur Radiol. 2016;26:4345–53. https://doi.org/10.1007/s00330-016-4308-4.

    Article  PubMed  Google Scholar 

  5. Fennessy N, Lee J, Shin J, Ho B, Ali SA, Paschkewitz R, et al. Frusemide aids diagnostic interpretation of (68) Ga-PSMA positron emission tomography/CT in men with prostate cancer. J Med Imaging Radiat Oncol. 2017;61:739–44. https://doi.org/10.1111/1754-9485.12625.

    Article  PubMed  Google Scholar 

  6. Haupt F, Dijkstra L, Alberts I, Sachpekidis C, Fech V, Boxler S, et al. (68)Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer-a modified protocol compared with the common protocol. Eur J Nucl Med Mol Imaging. 2020;47:624–31. https://doi.org/10.1007/s00259-019-04548-5.

    CAS  Article  PubMed  Google Scholar 

  7. Uprimny C, Bayerschmidt S, Kroiss AS, Fritz J, Nilica B, Svirydenka A, et al. Impact of forced diuresis with furosemide and hydration on the halo artefact and intensity of tracer accumulation in the urinary bladder and kidneys on [(68)Ga]Ga-PSMA-11-PET/CT in the evaluation of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2021;48:123–33. https://doi.org/10.1007/s00259-020-04846-3.

    CAS  Article  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. Rodnick ME, Sollert C, Stark D, Clark M, Katsifis A, Hockley BG, et al. Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target. EJNMMI Radiopharm Chem. 2020;5:25. https://doi.org/10.1186/s41181-020-00106-9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Giesel FL, Hadaschik B, Cardinale J, Radtke J, Vinsensia M, Lehnert W, et al. F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2017;44:678–88. https://doi.org/10.1007/s00259-016-3573-4.

    CAS  Article  PubMed  Google Scholar 

  11. Debowski M, Gulhane B, Ramsay SC, Thomas P, Garcia P, Latter M, et al. Prospective intra-individual blinded comparison of 18F-PSMA-1007 and 68Ga-PSMA-11 PET/CT imaging in patients with confirmed prostate cancer. Intern Med J. 2019;49:27.

    Google Scholar 

  12. Giesel FL, Knorr K, Spohn F, Will L, Maurer T, Flechsig P, et al. Detection efficacy of 18F-PSMA-1007 PET/CT in 251 patients with biochemical recurrence of prostate cancer after radical prostatectomy. J Nucl Med. 2019;60:362–8. https://doi.org/10.2967/jnumed.118.212233.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Kuten J, Fahoum I, Savin Z, Shamni O, Gitstein G, Hershkovitz D, et al. Head-to-head comparison of 68 Ga-PSMA-11 with 18 F-PSMA-1007 PET/CT in staging prostate cancer using histopathology and Immunohistochemical Analysis as a reference standard. J Nucl Med. 2020;61:527.

    CAS  Article  Google Scholar 

  14. Rahbar K, Afshar-Oromieh A, Seifert R, Wagner S, Schäfers M, Bögemann M, et al. Diagnostic performance of 18F-PSMA-1007 PET/CT in patients with biochemical recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:2055–61. https://doi.org/10.1007/s00259-018-4089-x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Alberts IL, Seide SE, Mingels C, Bohn KP, Shi K, Zacho HD, et al. Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis. Eur J Nucl Med Mol Imaging. 2021. https://doi.org/10.1007/s00259-021-05210-9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rauscher I, Kronke M, Konig M, Gafita A, Maurer T, Horn T, et al. Matched-pair comparison of (68)Ga-PSMA-11 PET/CT and (18)F-PSMA-1007 PET/CT: frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy. J Nucl Med. 2020;61:51–7. https://doi.org/10.2967/jnumed.119.229187.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Rowe SP, Pienta KJ, Pomper MG, Gorin MA. Proposal for a structured reporting system for prostate-specific membrane antigen-targeted PET imaging: PSMA-RADS Version 1.0. J Nucl Med. 2018;59:479. https://doi.org/10.2967/jnumed.117.195255.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S. https://doi.org/10.2967/jnumed.108.057307.

    CAS  Article  PubMed  Google Scholar 

  19. StataCorp. Stata Statistical Software: Release 15. College Station: StataCorp LLC; 2017.

  20. Kuten J, Dekalo S, Mintz I, Yossepowitch O, Mano R, Even-Sapir E. The significance of equivocal bone findings in staging PSMA imaging in the preoperative setting: validation of the PSMA-RADS version 1.0. EJNMMI Res. 2021;11:3. https://doi.org/10.1186/s13550-020-00745-8.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yin Y, Werner RA, Higuchi T, Lapa C, Pienta KJ, Pomper MG, et al. Follow-up of lesions with equivocal radiotracer uptake on PSMA-targeted PET in patients with prostate cancer: predictive values of the PSMA-RADS-3A and PSMA-RADS-3B categories. J Nucl Med. 2019;60:511–6. https://doi.org/10.2967/jnumed.118.217653.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 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;31:578–83. https://doi.org/10.1053/hp.2000.6698.

    CAS  Article  PubMed  Google Scholar 

  23. Lamothe F, Kovi J, Heshmat MY, Green EJ. Dissemination of prostatic carcinoma: an autopsy study. J Natl Med Assoc. 1986;78:1083–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Agheli A, Patsiornik Y, Chen Y, Chaudhry MR, Gerber H, Wang JC. Prostate carcinoma, presenting with a solitary osteolytic bone lesion to the right hip. Radiol Case Rep. 2009;4. https://doi.org/10.2484/rcr.v4i4.288.

  25. Wang C, Shen Y. Study on the distribution features of bone metastases in prostate cancer. Nucl Med Commun. 2012;33:379–83. https://doi.org/10.1097/MNM.0b013e3283504528.

    Article  PubMed  Google Scholar 

  26. Chen MY, Franklin A, Yaxley J, Gianduzzo T, McBean R, Wong D, et al. Solitary rib lesions showing prostate-specific membrane antigen (PSMA) uptake in pre-treatment staging 68Ga-PSMA-11 positron emission tomography scans for men with prostate cancer: benign or malignant? BJU Int. 2020;126:396–401. https://doi.org/10.1111/bju.15152.

    CAS  Article  PubMed  Google Scholar 

  27. Hofman MS, Hicks RJ, Maurer T, Eiber M. Prostate-specific membrane antigen PET: clinical utility in prostate cancer, normal patterns, pearls, and pitfalls. Radiographics. 2018;38:200. https://doi.org/10.1148/rg.2018170108.

    Article  PubMed  Google Scholar 

  28. Keidar Z, Gill R, Goshen E, Israel O, Davidson T, Morgulis M, et al. 68Ga-PSMA PET/CT in prostate cancer patients - patterns of disease, benign findings and pitfalls. Cancer Imaging (BioMed). 2018;18. https://doi.org/10.1186/s40644-018-0175-3.

  29. Sheikhbahaei S, Afshar-Oromieh A, Eiber M, Solnes L, Javadi M, Ross A, 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. https://doi.org/10.1007/s00259-017-3780-7.

    Article  PubMed  Google Scholar 

  30. Shetty D, Patel D, Le K, Bui C, Mansberg R. Pitfalls in gallium-68 PSMA PET/CT interpretation-a pictorial review. Tomography. 2018;4:182–93. https://doi.org/10.18383/j.tom.2018.00021.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cardinale J, Schäfer M, Benešová M, Bauder-Wüst U, Leotta K, Eder M, et al. Preclinical evaluation of 18F-PSMA-1007, a new prostate-specific membrane antigen ligand for prostate cancer imaging. J Nucl Med. 2017;58:425–31. https://doi.org/10.2967/jnumed.116.181768.

    CAS  Article  PubMed  Google Scholar 

  32. Eiber M, Herrmann K, Calais J, Hadaschik B, Giesel FL, Hartenbach M, et al. Prostate cancer molecular imaging standardized evaluation (PROMISE): proposed miTNM classification for the interpretation of PSMA-ligand PET/CT. J Nucl Med. 2018;59:469–78. https://doi.org/10.2967/jnumed.117.198119.

    Article  PubMed  Google Scholar 

  33. Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. The Lancet. 2018;392:2353–66. https://doi.org/10.1016/S0140-6736(18)32486-3.

    Article  Google Scholar 

  34. Rowe SP, Macura KJ, Mena E, Blackford AL, Nadal R, Antonarakis ES, et al. PSMA-Based [18F]DCFPyL PET/CT Is superior to conventional imaging for lesion detection in patients with metastatic prostate cancer. Mol Imaging Biol. 2016;18:411–9. https://doi.org/10.1007/s11307-016-0957-6.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. Adams MC, Turkington TG, Wilson JM, Wong TZ. A systematic review of the factors affecting accuracy of SUV measurements. AJR Am J Roentgenol. 2010;195:310–20. https://doi.org/10.2214/AJR.10.4923.

    Article  PubMed  Google Scholar 

  36. Aide N, Lasnon C, Veit-Haibach P, Sera T, Sattler B, Boellaard R. EANM/EARL harmonization strategies in PET quantification: from daily practice to multicentre oncological studies. Eur J Nucl Med Mol Imaging. 2017;44:17–31. https://doi.org/10.1007/s00259-017-3740-2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Ku M-T, Chen Y-L, Yang B-H, Huang W-S, Liu R-S. Comparison between SiPM-based and conventional PMT-based PET scanners in different reconstruction algorithm using ACR phantom. J Nucl Med. 2020;61:3089.

    Google Scholar 

Download references

Funding

No funding was received for conducting this study. Matthew J Roberts is supported by a Clinician Research Fellowship from the Metro North Office of Research, Queensland Health, and a Doctor in Training Research Scholarship from Avant Mutual Group Pty Ltd.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Evyn G. Arnfield.

Ethics declarations

Ethics approval and consent to participate

This retrospective audit was approved by the institutional review board of the Royal Brisbane and Women’s Hospital the need for written informed consent was waived.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Evyn G. Arnfield as first author.

This article is part of the Topical Collection on Oncology - Genitourinary

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 14 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Arnfield, E.G., Thomas, P.A., Roberts, M.J. et al. Clinical insignificance of [18F]PSMA-1007 avid non-specific bone lesions: a retrospective evaluation. Eur J Nucl Med Mol Imaging 48, 4495–4507 (2021). https://doi.org/10.1007/s00259-021-05456-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-021-05456-3

Keywords

  • Prostate cancer
  • [18F]PSMA-1007 PET
  • Bone metastases