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New frontiers in prostate cancer imaging: clinical utility of prostate-specific membrane antigen positron emission tomography

  • Urology - Review
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Abstract

Prostate-specific membrane antigen positron emission tomography (PSMA PET) is a relatively new method of imaging prostate cancer that increases diagnostic accuracy in detecting and guiding management in various stages of the disease pathway. Gallium-68-labelled PSMA PET has increased the sensitivity of detection of disease recurrence at low PSA levels, thus allowing an optimal window for salvage treatment. Apart from its use in disease recurrence, PSMA PET has the potential for increasing sensitivity and specificity for primary tumour localisation and in detecting lymph node disease, leading to a more accurate initial staging of the condition. In advanced disease, the use of PSMA PET may be able to assess response to treatment and also guide treatment with radionuclide therapy. Newer ligands under development might provide avenues for theranostic or personalised therapy applications with early data showing high PSA response rates. The rate of translation of PSMA PET into clinical practice has been remarkable. The use of this modality is likely to increase with future efforts to modify the radiotracer including 18F labelling to improve availability.

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References

  1. Umbehr MH, Müntener M, Hany T, Sulser T, Bachmann LM (2013) The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur Urol 64(1):106–117

    Article  PubMed  Google Scholar 

  2. Maurer T, Eiber M, Schwaiger M, Gschwend JE (2016) Current use of PSMA-PET in prostate cancer management. Nat Rev Urol 13(4):226–235

    Article  CAS  PubMed  Google Scholar 

  3. Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, Holland-Letz T, Giesel FL, Kratochwil C, Haufe S, Haberkorn U, Zechmann CM (2013) PET imaging with a [68 Ga]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 40(4):486–495

    Article  CAS  PubMed  Google Scholar 

  4. Baccala A, Sercia L, Li J, Heston W, Zhou M (2007) Expression of prostate-specific membrane antigen in tumor-associated neovasculature of renal neoplasms. Urology 70(2):385–390

    Article  PubMed  Google Scholar 

  5. Chang SS, Reuter VE, Heston WD, Gaudin PB (2001) Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen. Urology 57(4):801–805

    Article  CAS  PubMed  Google Scholar 

  6. Chang S, Reuter V, Heston W, Bander N, Grauer L, Gaudin P (1999) Five different anti-prostate-specific membrane antigen (PSMA) antibodies conform PSMA expression in tumor-associated neovasculature. Cancer Res 59(13):3192–3198

    CAS  PubMed  Google Scholar 

  7. Sathekge M, Modiselle M, Vorster M, Mokgoro N, Nyakale N, Mokaleng B et al (2015) 68 Ga-PSMA imaging of metastatic breast cancer. Eur J Nucl Med Mol Imaging 42(9):1482–1483

    Article  PubMed  Google Scholar 

  8. Wernicke AG, Varma S, Greenwood EA, Christos PJ, Chao KS, Liu H et al (2014) Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers. APMIS 122(6):482–489

    Article  CAS  PubMed  Google Scholar 

  9. Nomura N, Pastorino S, Jiang P, Lambert G, Crawford JR, Gymnopoulos M et al (2014) Prostate-specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int 14(1):26

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rauscher I, Maurer T, Fendler WP, Sommer WH, Schwaiger M, Eiber M (2016) 68 Ga-PSMA ligand PET/CT in patients with prostate cancer: how we review and report. Cancer Imaging 16(1):14

    Article  PubMed  PubMed Central  Google Scholar 

  11. Pfister D, Bolla M, Briganti A, Carroll P, Cozzarini C, Joniau S, van Poppel H, Roach M, Stephenson A, Wiegel T, Zelefsky MJ (2014) Early salvage radiotherapy following radical prostatectomy. Eur Urol 65(6):1034–1043

    Article  PubMed  Google Scholar 

  12. King CR (2012) The timing of salvage radiotherapy after radical prostatectomy: a systematic review. Int J Radiat Oncol Biol Phys 84(1):104–111

    Article  PubMed  Google Scholar 

  13. Castellucci P, Fuccio C, Rubello D, Schiavina R, Santi I, Nanni C, Allegri V, Montini GC, Ambrosini V, Boschi S, Martorana G, Marzola MC, Fanti S (2011) Is there a role for 11C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml? Eur J Nucl Med Mol Imaging 38(1):55–63

    Article  PubMed  Google Scholar 

  14. Castellucci P, Picchio M (2013) 11C-choline PET/CT and PSA kinetics. Eur J Nucl Med Mol Imaging 40(Suppl 1):S36–S40

    Article  PubMed  Google Scholar 

  15. Graute V, Jansen N, Ubleis C, Seitz M, Hartenbach M, Scherr MK, Thieme S, Cumming P, Klanke K, Tiling R, Bartenstein P, Hacker M (2012) Relationship between PSA kinetics and [18F]fluorocholine PET/CT detection rates of recurrence in patients with prostate cancer after total prostatectomy. Eur J Nucl Med Mol Imaging 39(2):271–282

    Article  CAS  PubMed  Google Scholar 

  16. Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, Holland-Letz T, Hadaschik BA, Giesel FL, Debus J, Haberkorn U (2014) 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 41(1):11–20

    Article  CAS  PubMed  Google Scholar 

  17. Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, Hruby G, Fogarty G, Jagavkar R, Kneebone A, Hickey A, Fanti S, Tarlinton L, Emmett L (2015) Prospective comparison of 18F-fluoromethylcholine versus 68 Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med 56(8):1185–1190

    Article  CAS  PubMed  Google Scholar 

  18. Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, Eisenhut M, Boxler S, Hadaschik BA, Kratochwil C, Weichert W, Kopka K, Debus J, Haberkorn U (2015) 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 42(2):197–209

    Article  CAS  PubMed  Google Scholar 

  19. Ceci F, Uprimny C, Nilica B, Geraldo L, Kendler D, Kroiss A, Bektic J, Horninger W, Lukas P, Decristoforo C, Castellucci P, Fanti S, Virgolini IJ (2015) (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 42(8):1284–1294

    Article  PubMed  Google Scholar 

  20. Ross JS, Sheehan CE, Fisher HA, Kaufman RP Jr, Kaur P, Gray K, Webb I, Gray GS, Mosher R, Kallakury BV (2003) Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res 9(17):6357–6362

    CAS  PubMed  Google Scholar 

  21. Turkbey B, Mani H, Shah V, Rastinehad AR, Bernardo M, Pohida T, Pang Y, Daar D, Benjamin C, McKinney YL, Trivedi H, Chua C, Bratslavsky G, Shih JH, Linehan WM, Merino MJ, Choyke PL, Pinto PA (2011) Multiparametric 3T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds. J Urol 186(5):1818–1824

    Article  PubMed  Google Scholar 

  22. Styles C, Ferris N, Mitchell C, Murphy D, Frydenberg M, Mills J, Pedersen J, Bergen N, Duchesne G (2014) Multiparametric 3T MRI in the evaluation of intraglandular prostate cancer: correlation with histopathology. J Med Imaging Radiat Oncol 58(4):439–448

    PubMed  Google Scholar 

  23. Budäus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, Graefen M, Steuber T, Rosenbaum C (2016) Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol 69(3):393–396

    Article  PubMed  Google Scholar 

  24. Chakraborty PS, Tripathi M, Agarwal KK, Kumar R, Vijay MK, Bal C (2015) Metastatic poorly differentiated prostatic carcinoma with neuroendocrine differentiation: negative on 68 Ga-PSMA PET/CT. Clin Nucl Med 40(2):e163–e166

    Article  PubMed  Google Scholar 

  25. Sweat SD, Pacelli A, Murphy GP, Bostwick DG (1998) Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology 52:637–640

    Article  CAS  PubMed  Google Scholar 

  26. Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, Wester HJ, Heck M, Kübler H, Beer AJ, Schwaiger M, Eiber M (2016) 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 195(5):1436–1443

    Article  PubMed  Google Scholar 

  27. Evangelista L, Guttilla A, Zattoni F, Muzzio PC, Zattoni F (2013) Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high- risk prostate cancer: a systematic literature review and meta-analysis. Eur Urol 63:1040–1048

    Article  PubMed  Google Scholar 

  28. Derlin T, Eiber M, Schwaiger M, Bengel FM (2016). Re: Budäus L, Leyh-Bannurah S-R, Salomon G, et al. (2016) Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur. Urol. 69:393–396. Eur. Urol. 70(2):e37–e38

  29. Lecouvet FE, El Mouedden J, Collette L, Coche E, Danse E, Jamar F, Machiels JP, Vande Berg B, Omoumi P, Tombal B (2012) Can whole-body magnetic resonance imaging with diffusion-weighted imaging replace Tc 99 m bone scanning and computed tomography for single-step detection of metastases in patients with high-risk prostate cancer? Eur Urol 62(1):68–75

    Article  PubMed  Google Scholar 

  30. Afshar-Oromieh A, Haberkorn U, Schlemmer HP, Fenchel M, Eder M, Eisenhut M, Hadaschik BA, Kopp-Schneider A, Röthke M (2014) Comparison of PET/CT and PET/MRI hybrid systems using a 68 Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur J Nucl Med Mol Imaging 41(5):887–897

    Article  CAS  PubMed  Google Scholar 

  31. Freitag MT, Radtke JP, Hadaschik BA, Kopp-Schneider A, Eder M, Kopka K, Haberkorn U, Roethke M, Schlemmer HP, Afshar-Oromieh A (2016) Comparison of hybrid (68)Ga-PSMA PET/MRI and (68)Ga-PSMA PET/CT in the evaluation of lymph node and bone metastases of prostate cancer. Eur J Nucl Med Mol Imaging 43(1):70–83

    Article  CAS  PubMed  Google Scholar 

  32. Schmittgen TD, Teske S, Vessella RL, True LD, Zakrajsek BA (2003) Expression of prostate specific membrane antigen and three alternatively spliced variants of PSMA in prostate cancer patients. Int J Cancer 107:323–329

    Article  CAS  PubMed  Google Scholar 

  33. Ahmadzadehfar H, Eppard E, Kürpig S, Fimmers R, Yordanova A, Schlenkhoff CD, Gärtner F, Rogenhofer S, Essler M (2016) Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate- resistant metastatic prostate cancer. Oncotarget 7:12477–12488

    PubMed  PubMed Central  Google Scholar 

  34. Kratochwil C, Giesel FL, Stefanova M, Benešová M, Bronzel M, Afshar-Oromieh A, Mier W, Eder M, Kopka K, Haberkorn U (2016) PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA- 617. J Nucl Med 57:1170–1176

    Article  PubMed  Google Scholar 

  35. Cho SY, Gage KL, Mease RC, Senthamizhchelvan S, Holt DP, Jeffrey-Kwanisai A, Endres CJ, Dannals RF, Sgouros G, Lodge M, Eisenberger MA, Rodriguez R, Carducci MA, Rojas C, Slusher BS, Kozikowski AP, Pomper MG (2012) Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular- weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med 53:1883–1891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rowe SP, Gage KL, Faraj SF, Macura KJ, Cornish TC, Gonzalez-Roibon N, Guner G, Munari E, Partin AW, Pavlovich CP, Han M, Carter HB, Bivalacqua TJ, Blackford A, Holt D, Dannals RF, Netto GJ, Lodge MA, Mease RC, Pomper MG, Cho SY (2015) F-DCFBC PET/CT for PSMA-based detection and characterization of primary prostate cancer. J Nucl Med 56(7):1003–1010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Szabo Z, Mena E, Rowe SP, Plyku D, Nidal R, Eisenberger MA, Antonarakis ES, Fan H, Dannals RF, Chen Y, Mease RC, Vranesic M, Bhatnagar A, Sgouros G, Cho SY, Pomper MG (2015) Initial evaluation of [F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol 17(4):565–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dietlein M, Kobe C, Kuhnert G, Stockter S, Fischer T, Schomäcker K, Schmidt M, Dietlein F, Zlatopolskiy BD, Krapf P, Richarz R, Neubauer S, Drzezga A, Neumaier B (2016) Comparison of [F]DCFPyL and [68 Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol 17(4):575–584

    Article  Google Scholar 

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Acknowledgements

Dr. Afaq is partly funded by the National Institute for Health Research University College London Hospitals Biomedical Research Centre and a London North West Healthcare Charitable Fund Grant.

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Authors and Affiliations

  1. Institute of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, Euston Road, London, UK

    Asim Afaq & Jamshed Bomanji

  2. Department of Radiology, London North West Healthcare NHS Trust, Watford Road, London, UK

    Asim Afaq

  3. Department of Urology, London North West Healthcare NHS Trust, Watford Road, London, UK

    Deepak Batura

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  1. Asim Afaq
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  2. Deepak Batura
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Correspondence to Deepak Batura.

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Afaq, A., Batura, D. & Bomanji, J. New frontiers in prostate cancer imaging: clinical utility of prostate-specific membrane antigen positron emission tomography. Int Urol Nephrol 49, 803–810 (2017). https://doi.org/10.1007/s11255-017-1541-y

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  • DOI: https://doi.org/10.1007/s11255-017-1541-y

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