Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Positron emission tomography (PET) radiotracers for prostate cancer imaging

Abstract

Imaging plays an increasing role in prostate cancer diagnosis and staging. Accurate staging of prostate cancer is required for optimal treatment planning. In detecting extraprostatic cancer and sites of early recurrence, traditional imaging methods (computed tomography, magnetic resonance imaging, radionuclide bone scan) have suboptimal performance. This leaves a gap between known disease recurrence as indicated by rising prostate-specific antigen and the ability to localize the recurrence on imaging. Novel positron emission tomography (PET) agents including radiolabeled choline, fluciclovine (18F-FACBC), and agents targeting prostate-specific membrane antigen are being developed and tested to increase diagnostic performance of non-invasive prostate cancer localization. When combined with CT or MRI, these tracers offer a combination of functional information and anatomic localization that is superior to conventional imaging methods. These PET radiotracers have varying mechanisms and excretion patterns affecting their pharmacokinetics and diagnostic performance, which will be reviewed in this article.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Siegel, R.L., K.D. Miller, and A. Jemal, Cancer statistics, 2019. 2019. 69(1): p. 7-34.

  2. 2.

    Li, R., et al., The use of PET/CT in prostate cancer. Prostate Cancer and Prostatic Diseases, 2018. 21(1): p. 4-21.

  3. 3.

    De Bruycker, A., et al., Prevalence and prognosis of low-volume, oligorecurrent, hormone-sensitive prostate cancer amenable to lesion ablative therapy. 2017. 120(6): p. 815-821.

  4. 4.

    Giannarini, G., et al., Will Image-guided Metastasis-directed Therapy Change the Treatment Paradigm of Oligorecurrent Prostate Cancer? European Urology, 2018. 74(2): p. 131-133.

  5. 5.

    Jadvar, H., Molecular imaging of prostate cancer: PET radiotracers. AJR. American journal of roentgenology, 2012. 199(2): p. 278-291.

  6. 6.

    Bednarova, S., et al., Positron emission tomography (PET) in primary prostate cancer staging and risk assessment. 2017, 2017. 6(3): p. 413-423.

  7. 7.

    Almuhaideb, A., N. Papathanasiou, and J. Bomanji, 18F-FDG PET/CT imaging in oncology. Annals of Saudi medicine, 2011. 31(1): p. 3-13.

  8. 8.

    Jadvar, H., FDG PET in Prostate Cancer. PET clinics, 2009. 4(2): p. 155-161.

  9. 9.

    Picchio, M., et al., Value of [11C]choline-Positron Emission Tomography for Re-Staging Prostate Cancer: A Comparison With [18F]fluorodeoxyglucose-Positron Emission Tomography. The Journal of Urology, 2003. 169(4): p. 1337-1340.

  10. 10.

    Ackerstaff, E., et al., Detection of Increased Choline Compounds with Proton Nuclear Magnetic Resonance Spectroscopy Subsequent to Malignant Transformation of Human Prostatic Epithelial Cells. 2001. 61(9): p. 3599-3603.

  11. 11.

    Wallitt, K.L., et al., Clinical PET Imaging in Prostate Cancer. 2017. 37(5): p. 1512-1536.

  12. 12.

    Umbehr, M.H., et al., The Role of 11C-Choline and 18F-Fluorocholine Positron Emission Tomography (PET) and PET/CT in Prostate Cancer: A Systematic Review and Meta-analysis. European Urology, 2013. 64(1): p. 106-117.

  13. 13.

    Cimitan, M., et al., [18F]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients. European Journal of Nuclear Medicine and Molecular Imaging, 2006. 33(12): p. 1387-1398.

  14. 14.

    Jadvar, H., Prostate cancer: PET with 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2011. 52(1): p. 81-89.

  15. 15.

    Fuccio, C., et al., Role of 11C-choline PET/CT in the restaging of prostate cancer patients showing a single lesion on bone scintigraphy. Annals of Nuclear Medicine, 2010. 24(6): p. 485-492.

  16. 16.

    Hövels, A.M., et al., The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clinical Radiology, 2008. 63(4): p. 387-395.

  17. 17.

    Evangelista, L., et al., Choline PET or PET/CT and Biochemical Relapse of Prostate Cancer: A Systematic Review and Meta-Analysis. 2013. 38(5): p. 305-314.

  18. 18.

    Guo, Y., et al., Diagnostic performance of choline PET/CT for the detection of bone metastasis in prostate cancer: A systematic review and meta-analysis. PLOS ONE, 2018. 13(9): p. e0203400.

  19. 19.

    Giovacchini, G., et al., Predictive factors of [11C]choline PET/CT in patients with biochemical failure after radical prostatectomy. European Journal of Nuclear Medicine and Molecular Imaging, 2010. 37(2): p. 301-309.

  20. 20.

    Castellucci, P., et al., 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? European Journal of Nuclear Medicine and Molecular Imaging, 2011. 38(1): p. 55-63.

  21. 21.

    Sakata, T., et al., L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathology International, 2009. 59(1): p. 7-18.

  22. 22.

    Oka, S., et al., A preliminary study of anti-1-amino-3-F-18-fluorocyclobutyl-1-carboxylic acid for the detection of prostate cancer. Journal of Nuclear Medicine, 2007. 48(1): p. 46-55.

  23. 23.

    Savir-Baruch, B., et al., Fluorine-18-Labeled Fluciclovine PET/CT in Clinical Practice: Factors Affecting the Rate of Detection of Recurrent Prostate Cancer. American Journal of Roentgenology, 2019: p. 1-8.

  24. 24.

    Odewole, O.A., et al., Recurrent prostate cancer detection with anti-3-[(18)F]FACBC PET/CT: comparison with CT. Eur J Nucl Med Mol Imaging, 2016. 43(10): p. 1773-83.

  25. 25.

    Kim, S.J. and S.W. Lee, The role of 18F-fluciclovine PET in the management of prostate cancer: a systematic review and meta-analysis. Clinical Radiology, 2019.

  26. 26.

    Turkbey, B., et al., Localized prostate cancer detection with 18F FACBC PET/CT: comparison with MR imaging and histopathologic analysis. Radiology, 2014. 270(3): p. 849-56.

  27. 27.

    Selnaes, K.M., et al., (18)F-Fluciclovine PET/MRI for preoperative lymph node staging in high-risk prostate cancer patients. Eur Radiol, 2018. 28(8): p. 3151-3159.

  28. 28.

    Pernthaler, B., et al., A Prospective Head-to-Head Comparison of 18F-Fluciclovine With 68 Ga-PSMA-11 in Biochemical Recurrence of Prostate Cancer in PET/CT. 2019. 44(10): p. e566-e573.

  29. 29.

    Nanni, C., et al., 18F-Fluciclovine PET/CT for the Detection of Prostate Cancer Relapse: A Comparison to 11C-Choline PET/CT. 2015. 40(8): p. e386-e391.

  30. 30.

    Wright, G.L., et al., Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urologic Oncology: Seminars and Original Investigations, 1995. 1(1): p. 18-28.

  31. 31.

    Martin, K.B., et al., Neuroendocrine differentiation of prostate cancer leads to PSMA suppression. Endocrine-Related Cancer, 2019. 26(2): p. 131-146.

  32. 32.

    Prasad, V., et al., Biodistribution of [68 Ga]PSMA-HBED-CC in Patients with Prostate Cancer: Characterization of Uptake in Normal Organs and Tumour Lesions. Molecular Imaging and Biology, 2016. 18(3): p. 428-436.

  33. 33.

    Koerber, S.A., et al., (68)Ga-PSMA-11 PET/CT in Primary and Recurrent Prostate Carcinoma: Implications for Radiotherapeutic Management in 121 Patients. J Nucl Med, 2018.

  34. 34.

    Calais, J., et al., (18)F-fluciclovine PET-CT and (68)Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncol, 2019. 20(9): p. 1286-1294.

  35. 35.

    Afshar-Oromieh, A., 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(8): p. 1258-1268.

  36. 36.

    Fendler, W.P., et al., Assessment of 68 Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol, 2019. 5(6): p. 856-863.

  37. 37.

    Afshar-Oromieh, A., et al., Impact of long-term androgen deprivation therapy on PSMA ligand PET/CT in patients with castration-sensitive prostate cancer. Eur J Nucl Med Mol Imaging, 2018. 45(12): p. 2045-2054.

  38. 38.

    Sterzing, F., et al., 68 Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of prostate cancer patients. European Journal of Nuclear Medicine and Molecular Imaging, 2016. 43(1): p. 34-41.

  39. 39.

    Gorin, M.A., M.G. Pomper, and S.P. Rowe, PSMA-targeted imaging of prostate cancer: the best is yet to come. 2016. 117(5): p. 715-716.

  40. 40.

    Sanchez-Crespo, A., Comparison of Gallium-68 and Fluorine-18 imaging characteristics in positron emission tomography. Applied Radiation and Isotopes, 2013. 76: p. 55-62.

  41. 41.

    Dietlein, M., et al., Comparison of [18F]DCFPyL and [68 Ga]Ga-PSMA-HBED-CC for PSMA-PET Imaging in Patients with Relapsed Prostate Cancer. Molecular Imaging and Biology, 2015. 17(4): p. 575-584.

  42. 42.

    Czarniecki, M., et al., Keeping up with the prostate-specific membrane antigens (PSMAs): an introduction to a new class of positron emission tomography (PET) imaging agents. 2018, 2018. 7(5): p. 831-843.

  43. 43.

    Rowe, S.P., et al., Comparison of Prostate-Specific Membrane Antigen-Based 18F-DCFBC PET/CT to Conventional Imaging Modalities for Detection of Hormone-Naive and Castration-Resistant Metastatic Prostate Cancer. J Nucl Med, 2016. 57(1): p. 46-53.

  44. 44.

    Harmon, S.A., et al., A Prospective Comparison of (18)F-Sodium Fluoride PET/CT and PSMA-Targeted (18)F-DCFBC PET/CT in Metastatic Prostate Cancer. J Nucl Med, 2018. 59(11): p. 1665-1671.

  45. 45.

    Wondergem, M., et al., 18F-DCFPyL PET/CT in primary staging of prostate cancer. 2018. 2(1): p. 26.

  46. 46.

    Rowe, S.P., et al., Prospective Evaluation of PSMA-Targeted (18)F-DCFPyL PET/CT in Men with Biochemical Failure after Radical Prostatectomy for Prostate Cancer. J Nucl Med, 2019.

  47. 47.

    Rowe, S.P., et al., PSMA-Based [18F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer. Molecular Imaging and Biology, 2016. 18(3): p. 411-419.

  48. 48.

    Giesel, F.L., et al., Detection Efficacy of (18)F-PSMA-1007 PET/CT in 251 Patients with Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy. J Nucl Med, 2019. 60(3): p. 362-368.

  49. 49.

    Kesch, C., et al., Intra-individual comparison of (18)F-PSMA-1007-PET/CT, multi-parametric MRI and radical prostatectomy specimen in patients with primary prostate cancer - a retrospective, proof of concept study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2017. 58.

  50. 50.

    Werner, R.A., et al., 18 F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging. Theranostics, 2020. 10(1): p. 1-16.

  51. 51.

    Dietlein, M., et al., Performance of the novel 18F-labeled prostate-specific membrane antigen-ligand PSMA-7 for PET/CT in prostate cancer patients. 2018. 59(supplement 1): p. 452.

  52. 52.

    Behr, S.C., et al., First-in-Human Phase I study of CTT1057, a Novel 18F Labeled Imaging Agent with Phosphoramidate Core Targeting Prostate Specific Membrane Antigen in Prostate Cancer. 2018.

  53. 53.

    Saga, T., et al., Initial evaluation of PET/CT with 18F‐FSU‐880 targeting prostate‐specific membrane antigen in prostate cancer patients. 2019. 110(2): p. 742.

  54. 54.

    Alonso, O., et al., PET/CT evaluation of prostate cancer patients with Al18F-PSMA-HBED-CC: a head-to-head comparison with 68 Ga-PSMA-HBED-CC. 2018. 59(supplement 1): p. 1499-1499.

  55. 55.

    Fraum, T.J., et al., Prostate cancer PET tracers: essentials for the urologist. Can J Urol, 2018. 25(4): p. 9371-9383.

  56. 56.

    Czernin, J., N. Satyamurthy, and C. Schiepers, Molecular mechanisms of bone 18F-NaF deposition. J Nucl Med, 2010. 51(12): p. 1826-9.

  57. 57.

    Sheikhbahaei, S., et al., 18F-NaF-PET/CT for the detection of bone metastasis in prostate cancer: a meta-analysis of diagnostic accuracy studies. Annals of Nuclear Medicine, 2019. 33(5): p. 351-361.

  58. 58.

    Chen, B., et al., Comparison of 18F-Fluciclovine PET/CT and 99mTc-MDP bone scan in detection of bone metastasis in prostate cancer. 2019. 40(9): p. 940-946.

  59. 59.

    Beheshti, M., et al., Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine PET/CT. J Nucl Med, 2016. 57(Suppl 3): p. 55S-60S.

  60. 60.

    Schirrmeister, H., Detection of bone metastases in breast cancer by positron emission tomography. Radiol Clin North Am, 2007. 45(4): p. 669-76, vi.

  61. 61.

    Jadvar, H. and P.M. Colletti, 18F-NaF/223RaCl2 theranostics in metastatic prostate cancer: treatment response assessment and prediction of outcome. The British Journal of Radiology, 2018. 91(1091): p. 20170948.

  62. 62.

    Poeppel, T.D., et al., 68 Ga-DOTATOC versus 68 Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. J Nucl Med, 2011. 52(12): p. 1864-70.

  63. 63.

    Morichetti, D., et al., Immunohistochemical expression and localization of somatostatin receptor subtypes in prostate cancer with neuroendocrine differentiation. Int J Immunopathol Pharmacol, 2010. 23(2): p. 511-22.

  64. 64.

    Gofrit, O.N., et al., PET/CT With 68 Ga-DOTA-TATE for Diagnosis of Neuroendocrine: Differentiation in Patients With Castrate-Resistant Prostate Cancer. 2017. 42(1): p. 1-6.

  65. 65.

    dos Santos, G., et al., Comparación intraindividual de la PET/TC con 68 Ga-DOTATATE vs. PET/TC con 11C-colina en pacientes con cáncer de próstata en recaída bioquímica: evaluación in vivo de la expresión de receptores de la somatostatina. Revista Española de Medicina Nuclear e Imagen Molecular, 2019. 38(1): p. 29-37.

  66. 66.

    Wang, J., 68 Ga-DOTATATE in Benign Prostate Hyperplasia. 2019. 44(3): p. 249-250.

Download references

Funding

This research is funded by intramural research program of NIH.

Author information

Correspondence to Baris Turkbey.

Ethics declarations

Conflict of interest

The authors have no disclosures.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Walker, S.M., Lim, I., Lindenberg, L. et al. Positron emission tomography (PET) radiotracers for prostate cancer imaging. Abdom Radiol (2020). https://doi.org/10.1007/s00261-020-02427-4

Download citation

Keywords

  • Prostate cancer
  • Prostate cancer imaging
  • Nuclear medicine
  • PET/CT
  • PET/MRI
  • PSMA