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Current use of PSMA–PET in prostate cancer management

Key Points

  • Prostate-specific membrane antigen (PSMA) is a promising and specific target for prostate cancer imaging

  • PSMA–PET imaging can add molecular information to multiparametric MRI and, therefore, delineate suspicious lesions for targeted biopsies, especially in patients whose biopsy samples are tumour-negative

  • PSMA–PET imaging shows increased specificity and sensitivity compared with current standard imaging (CT, MRI and bone scintigraphy) in patients with primary intermediate-risk or high-risk prostate cancer

  • PSMA–PET imaging improves detection of metastatic lesions even at low serum PSA values in biochemically recurrent prostate cancer

  • Enhanced detection of prostate cancer lesions might enable improved patient-tailored therapy planning and, therefore, lead to improved therapy outcomes

Abstract

Currently, the findings of imaging procedures used for detection or staging of prostate cancer depend on morphology of lymph nodes or bone metabolism and do not always meet diagnostic needs. Prostate-specific membrane antigen (PSMA), a transmembrane protein that has considerable overexpression on most prostate cancer cells, has gained increasing interest as a target molecule for imaging. To date, several small compounds for labelling PSMA have been developed and are currently being investigated as imaging probes for PET with the 68Ga-labelled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC being the most widely studied agent. 68Ga-PSMA–PET imaging in combination with multiparametric MRI (mpMRI) might provide additional molecular information on cancer localization within the prostate. In patients with primary prostate cancer of intermediate-risk to high-risk, PSMA-based imaging has been reported to improve detection of metastatic disease compared with CT or mpMRI, rendering additional cross-sectional imaging or bone scintigraphy unnecessary. Furthermore, in patients with biochemically recurrent prostate cancer, use of 68Ga-PSMA–PET imaging has been shown to increase detection of metastatic sites, even at low serum PSA values, compared with conventional imaging or PET examination with different tracers. Thus, although current knowledge is still limited and derived mostly from retrospective series, PSMA-based imaging holds great promise to improve prostate cancer management.

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Figure 1: The structure of prostate-specific membrane antigen (PSMA), its binding sites for PSMA ligands and the most frequently used antibodies.
Figure 2: 68Ga-PSMA–PET–MRI of a 50-year-old patient who had a rising serum PSA value (16 ng/ml at imaging) and two tumour-negative previous biopsy samples.
Figure 3: 68Ga-PSMA–PET–CT of a 52-year-old patient with primary prostate cancer (serum PSA value of 19 ng/ml and Gleason score 7 at biopsy).
Figure 4: 68Ga-PSMA–PET–CT of a 73-year-old patient with recurrent prostate cancer after radical prostatectomy (initial Gleason score 9) and local salvage radiotherapy.
Figure 5: Imaging of 65-year-old patient with prostate cancer and diffuse bone metastases.
Figure 6: 68Ga-PSMA–PET–CT of a 74-year-old patient with recurrent prostate cancer (initial Gleason score 7) after radical prostatectomy and local salvage radiotherapy with rising serum PSA value (1.76 ng/ml at the time of assessment).

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T.M. and M.E. contributed equally to the manuscript, researched data for and wrote the article. All authors made a substantial contribution to discussions of content and edited the manuscript before submission.

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Correspondence to Tobias Maurer.

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T.M. declares a familial association with Celgene® (Celgene Corporation, USA); grants or funding from Acelity® (KCI Licensing, Inc.), Bayer® (Bayer Aktiengesellschaft, Germany) and Takeda Oncology® (Takeda Pharmaceutical Company Limited, Japan); consultation for DLR® (Deutsches Luft-und Raumfahrtzentrum, Germany) and honoraria from Astellas® (Astellas US LLC, USA), Janssen Cilag (Johnson & Johnson, USA) and Sanofi® (Sanofi Corporation, France). M.E. declares grants or funding from Bayer® and honoraria Astellas® and Janssen Cilag. M.S. and J.E.G. declare no competing interests.

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Maurer, T., Eiber, M., Schwaiger, M. et al. Current use of PSMA–PET in prostate cancer management. Nat Rev Urol 13, 226–235 (2016). https://doi.org/10.1038/nrurol.2016.26

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