Abstract
Purpose
Dual-time point PET/CT scanning with [68Ga]Ga-PSMA-11 in the diagnosis of prostate cancer (PC) has been advanced as a method to increase detection of PC lesions, particularly at early stages of biochemical recurrence and as a potential means to aid the discrimination between benign and pathological prostate-specific membrane antigen (PSMA) uptake. However, the assumption that all PC lesions uniformly exhibit increasing tracer uptake at delayed imaging has not yet been investigated, which this present study aims to address.
Methods
One hundred consecutive patients with biochemically recurrent PC who received standard and late [68Ga]Ga-PSMA-11 PET/CT (by local protocol at 1.5 h “standard” and 2.5 h p.i. “late”) underwent retrospective evaluation. All lesions with a tracer uptake above local background were analysed with regard to their maximum standardised uptake values at standard and late images (SUVmax) and characterised according to their morphological characteristics.
Results
Seventy-nine of 100 patients had PSMA-positive scans, in whom a total of 185 individual PSMA-positive lesions were identified. These were morphologically characterised as bone lesions (n = 48), solid organ lesions (n = 3), lymph node (LN) lesions (n = 78) and locally recurrent lesions in the prostatic fossa or seminal vesicles (n = 56). The relative uptake between standard and late imaging was considered; all lesions classified as local recurrence presented with increasing (86%) or stable patterns of tracer uptake (14%). In contrast, only 58% of bone lesions exhibited increasing tracer uptake, with 21% exhibiting a stable pattern and 21% exhibiting a decreasing tracer uptake at late imaging.
Conclusion
A heterogeneous pattern of dynamic tracer uptake was observed, with a largely increasing pattern observed for locally recurrent lesions and lymph nodes and a significant proportion of bone lesions exhibiting decreasing tracer uptake. The results are of significance not only in the imaging and identification of PC lesions, but they also have implications for PSMA-directed ligand therapy.
Similar content being viewed by others
References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30. https://doi.org/10.3322/caac.21387.
Fossati N, Karnes RJ, Colicchia M, Boorjian SA, Bossi A, Seisen T, et al. Impact of early salvage radiation therapy in patients with persistently elevated or rising prostate-specific antigen after radical prostatectomy. Eur Urol. 2017. https://doi.org/10.1016/j.eururo.2017.07.026.
Israeli RS, Powell CT, Corr JG, Fair WR, Heston WDW. Expression of the prostate-specific membrane antigen. Cancer Res. 1994;54:1807.
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;41:11–20. https://doi.org/10.1007/s00259-013-2525-5.
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;44:1258–68. https://doi.org/10.1007/s00259-017-3711-7.
Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid (68)Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74. https://doi.org/10.2967/jnumed.115.154153.
Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. 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. 2015;42:197–209. https://doi.org/10.1007/s00259-014-2949-6.
Virgolini I, Decristoforo C, Haug A, Fanti S, Uprimny C. Current status of theranostics in prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:471–95. https://doi.org/10.1007/s00259-017-3882-2.
Chang SS. Overview of prostate-specific membrane antigen. Rev Urol. 2004;6:S13–S8.
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;40:486–95. https://doi.org/10.1007/s00259-012-2298-2.
Afshar-Oromieh A, Sattler LP, Steiger K, Holland-Letz T, da Cunha ML, Mier W, et al. Tracer uptake in mediastinal and paraaortal thoracic lymph nodes as a potential pitfall in image interpretation of PSMA ligand PET/CT. Eur J Nucl Med Mol Imaging. 2018;45:1179–87. https://doi.org/10.1007/s00259-018-3965-8.
Krohn T, Verburg FA, Pufe T, Neuhuber W, Vogg A, Heinzel A, et al. [(68)Ga]PSMA-HBED uptake mimicking lymph node metastasis in coeliac ganglia: an important pitfall in clinical practice. Eur J NuclMed Mol Imaging. 2015;42:210–4. https://doi.org/10.1007/s00259-014-2915-3.
Werner RA, Sheikhbahaei S, Jones KM, Javadi MS, Solnes LB, Ross AE, et al. Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted (18)F-DCFPyL in peripheral ganglia. Ann Nucl Med. 2017;31:696–702. https://doi.org/10.1007/s12149-017-1201-4.
Kanthan GL, Hsiao E, Vu D, Schembri GP. Uptake in sympathetic ganglia on 68Ga-PSMA-HBED PET/CT: a potential pitfall in scan interpretation. J Med Imaging Radiat Oncol. 2017;61:732–8. https://doi.org/10.1111/1754-9485.12622.
Hubble D, Robins P. RE: Uptake in sympathetic ganglia on 68Ga-PSMA-HBED PET/CT: a potential pitfall in scan interpretation. J Med Imaging Radiat Oncol. 2018;62:377–8. https://doi.org/10.1111/1754-9485.12739.
Rischpler C, Beck TI, Okamoto S, Schlitter AM, Knorr K, Schwaiger M, et al. (68)Ga-PSMA-HBED-CC uptake in cervical, coeliac and sacral ganglia as an important pitfall in prostate cancer PET imaging. J Nucl Med. 2018. https://doi.org/10.2967/jnumed.117.204677.
Afshar-Oromieh A, Sattler LP, Mier W, Hadaschik BA, Debus J, Holland-Letz T, et al. The clinical impact of additional late PET/CT imaging with (68)Ga-PSMA-11 (HBED-CC) in the diagnosis of prostate cancer. J Nucl Med. 2017;58:750–5. https://doi.org/10.2967/jnumed.116.183483.
Afshar-Oromieh A, Hetzheim H, Kubler W, Kratochwil C, Giesel FL, Hope TA, et al. Radiation dosimetry of (68)Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing. Eur J Nucl Med Mol Imaging. 2016;43:1611–20. https://doi.org/10.1007/s00259-016-3419-0.
Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, et al. The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med. 2015;56:1697–705. https://doi.org/10.2967/jnumed.115.161299.
Eder M, Neels O, Muller M, Bauder-Wust U, Remde Y, Schafer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals (Basel). 7:779–96. https://doi.org/10.3390/ph7070779.
Sachpekidis C, Baumer P, Kopka K, Hadaschik BA, Hohenfellner M, Kopp-Schneider A, et al. (68)Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:904–12. https://doi.org/10.1007/s00259-018-3936-0.
Lodge MA. Repeatability of SUV in oncologic (18)F-FDG PET. J Nucl Med. 2017;58:523–32. https://doi.org/10.2967/jnumed.116.186353.
Osborne JR, Kalidindi TM, Punzalan BJ, Gangangari K, Spratt DE, Weber WA, et al. Repeatability of [(68)Ga]DKFZ11-PSMA PET scans for detecting prostate-specific membrane antigen-positive prostate cancer. Mol Imaging Biol. 2017;19:944–51. https://doi.org/10.1007/s11307-017-1091-9.
Rahbar K, Afshar-Oromieh A, Seifert R, Wagner S, Schafers M, Bogemann M, et al. Diagnostic performance of (18)F-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.
Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. (68)Ga-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.
Sahlmann C-O, Meller B, Bouter C, Ritter CO, Ströbel P, Lotz J, et al. Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma. Eur J Nucl Med Mol Imaging. 2016;43:898–905. https://doi.org/10.1007/s00259-015-3251-y.
Bialek EJ, Malkowski B. Celiac ganglia: can they be misinterpreted on multimodal 68Ga-PSMA-11 PET/MR? Nucl Med Commun. 2019;40:175–84. https://doi.org/10.1097/MNM.0000000000000944.
Schillaci O, Urbano N. Digital PET/CT: a new intriguing chance for clinical nuclear medicine and personalized molecular imaging. Eur J Nucl Med Mol Imaging. 2019. https://doi.org/10.1007/s00259-019-04300-z.
Giesel FL, Knorr K, Spohn F, Will L, Maurer T, Flechsig P, 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;60:362–8. https://doi.org/10.2967/jnumed.118.212233.
Fendler WP, Calais J, Eiber M, Flavell RR, Mishoe A, Feng FY, et al. Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial. JAMA Oncol. 2019. https://doi.org/10.1001/jamaoncol.2019.0096.
Woythal N, Arsenic R, Kempkensteffen C, Miller K, Janssen JC, Huang K, et al. Immunohistochemical validation of PSMA expression measured by (68)Ga-PSMA PET/CT in primary prostate cancer. J Nucl Med. 2018;59:238–43. https://doi.org/10.2967/jnumed.117.195172.
Sachpekidis C, Kopka K, Eder M, Hadaschik BA, Freitag MT, Pan L, et al. 68Ga-PSMA-11 dynamic PET/CT imaging in primary prostate cancer. Clin Nucl Med. 2016;41:e473–e9. https://doi.org/10.1097/RLU.0000000000001349.
Rajasekaran SA, Anilkumar G, Oshima E, Bowie JU, Liu H, Heston W, et al. A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. Mol Biol Cell. 2003;14:4835–45. https://doi.org/10.1091/mbc.e02-11-0731.
Budäus L, Leyh-Bannurah S-R, Salomon G, Michl U, Heinzer H, Huland H, et al. Initial experience of 68Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol. 2016;69:393–6. https://doi.org/10.1016/j.eururo.2015.06.010.
Wieser G, Popp I, Christian Rischke H, Drendel V, Grosu AL, Bartholoma M, et al. Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist (68)Ga-RM2: preliminary results in patients with negative or inconclusive [(18)F]Fluoroethylcholine-PET/CT. Eur J Nucl Med Mol Imaging. 2017;44:1463–72. https://doi.org/10.1007/s00259-017-3702-8.
EANM’15, 28th Annual EANM Congress of the European Association of Nuclear Medicine 2015, 10-14 October 2015, Hamburg, Germany. European journal of nuclear medicine and molecular imaging. 2015;42 Suppl 1:S1-924. https://doi.org/10.1007/s00259-015-3198-z.
Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive (68)Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70:926–37. https://doi.org/10.1016/j.eururo.2016.06.021.
van Sluis JJ, de Jong J, Schaar J, Noordzij W, van Snick P, Dierckx R, et al. Performance characteristics of the digital Biograph Vision PET/CT system. J Nucl Med. 2019. https://doi.org/10.2967/jnumed.118.215418.
Acknowledgements
This thesis forms part of the doctorial thesis of I Alberts.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
All patients published in this manuscript signed a written informed consent form for the purpose of anonymised evaluation and the publication of their data. This evaluation was approved by the ethics committee of the University of Bern (KEK-Nr. 2018-00299).
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Oncology – Genitourinary
Electronic supplementary material
ESM 1
(DOCX 12 kb)
Rights and permissions
About this article
Cite this article
Alberts, I., Sachpekidis, C., Gourni, E. et al. Dynamic patterns of [68Ga]Ga-PSMA-11 uptake in recurrent prostate cancer lesions. Eur J Nucl Med Mol Imaging 47, 160–167 (2020). https://doi.org/10.1007/s00259-019-04545-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-019-04545-8