Optimal time-point for 68Ga-PSMA-11 PET/CT imaging in assessment of prostate cancer: feasibility of sterile cold-kit tracer preparation?

  • Mohsen Beheshti
  • Zeinab Paymani
  • Joana Brilhante
  • Hans Geinitz
  • Daniela Gehring
  • Thomas Leopoldseder
  • Ludovic Wouters
  • Christian Pirich
  • Wolfgang Loidl
  • Werner Langsteger
Original Article



In this prospective study, we evaluated the optimal time-point for 68Ga-PSMA-11 PET/CT acquisition in the assessment of prostate cancer. We also examined, for the first time the feasibility of tracer production using a PSMA-11 sterile cold-kit in the clinical workflow of PET/CT centres.


Fifty prostate cancer patients (25 staging, 25 biochemical recurrence) were enrolled in this study. All patients received an intravenous dose of 2.0 MBq/kg body weight 68Ga-PSMA-11 prepared using a sterile cold kit (ANMI SA, Liege, Belgium), followed by an early (20 min after injection) semi-whole-body PET/CT scan and a standard-delay (100 min after injection) abdominopelvic PET/CT scan. The detection rates with 68Ga-PSMA-11 were compared between the two acquisitions. The pattern of physiological background activity and tumour to background ratio were also analysed.


The total preparation time was reduced to 5 min using the PSMA-11 sterile cold kit, which improved the final radionuclide activity by about 30% per single 68Ge/68Ga generator elution. Overall, 158 pathological lesions were analysed in 45 patients (90%) suggestive of malignancy on both (early and standard-delay) 68Ga-PSMA PET/CT images. There was a significant (p < 0.001) increase in SUVmax on delayed images in suspicious prostates (11.6 ± 8.2 to 14.8 ± 1.0) and lymph nodes (LNs; 9.7 ± 5.9 to 12.3 ± 8.8), while bone lesions showed no significant increase (8.5 ± 5.6 to 9.2 ± 7.0, p = 0.188). However, the SUVmax of suspicious lesions on early images was adequate to support the criteria for correct interpretation (mean SUVmax 9.83 ± 6.7).In 26 of 157 lesions, but a decrease in SUV was seen, mostly in subcentimetre lesions in patients with multiple metastases. However, it did not affect the staging of the disease or patient management. The tumour to background ratio of primary prostate lesions and LNs showed a significant (p < 0.001) increase from the early to the standard-delay acquisition, but no significant increase was seen in bony lesions (p = 0.11).


The PSMA-11 sterile cold kit seems to be feasible for use in routine clinical practice, and it has a shorter radionuclide preparation time and is less operator-dependent than the synthesizer-based production method. In addition, early 68Ga-PSMA-11 PET/CT imaging seems to provide a detection rate comparable with that of standard-delay imaging. Furthermore, the shorter preparation time using the 68Ga-PSMA-11 sterile cold kit and promising value of early PET/CT scanning could allow tailoring of imaging protocols which may reduce the costs and improve the time efficiency in PET/CT centres.


68Ga-PSMA-11 PET/CT Sterile cold kit Dual-phase acquisition Detection rate 


Compliance with ethical standards

Conflicts of interest

Joana Brilhante and Ludovic Wouters are employees of ANMI SA, Liege, Belgium.

Mohsen Beheshti, Zeinab Paymani, Hans Geinitz, Daniela Gehring, Thomas Leopoldseder, Christian Pirich, Wolfgang Loidl and Werner Langsteger declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMedGoogle Scholar
  3. 3.
    Chang AJ, Autio KA, Roach M 3rd, Scher HI. High-risk prostate cancer-classification and therapy. Nat Rev Clin Oncol. 2014;11(6):308–23.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Stattin K, Sandin F, Bratt O, Lambe M. The risk of distant metastases and cancer specific survival in men with serum prostate specific antigen values above 100 ng/ml. J Urol. 2015;194(6):1594–600.CrossRefPubMedGoogle Scholar
  5. 5.
    Van Poppel H, Vekemans K, Da Pozzo L, et al. Radical prostatectomy for locally advanced prostate cancer: results of a feasibility study (EORTC 30001). Eur J Cancer. 2006;42(8):1062–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Rowe SP, Macura KJ, Ciarallo A, 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):46–53.CrossRefPubMedGoogle Scholar
  7. 7.
    Beheshti M, Vali R, Waldenberger P, et al. Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET/CT: a comparative study. Eur J Nucl Med Mol Imaging. 2008;35(10):1766–74.CrossRefPubMedGoogle Scholar
  8. 8.
    Sterzing F, Kratochwil C, Fiedler H, et al. 68Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2016;43(1):34–41.CrossRefPubMedGoogle Scholar
  9. 9.
    Beheshti M, Haim S, Zakavi R, et al. Impact of 18F-choline PET/CT in prostate cancer patients with biochemical recurrence: influence of androgen deprivation therapy and correlation with PSA kinetics. J Nucl Med. 2013;54(6):833–40.CrossRefPubMedGoogle Scholar
  10. 10.
    Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56(5):668–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Kwee SA, Coel MN, Lim J. Detection of recurrent prostate cancer with 18F-fluorocholine PET/CT in relation to PSA level at the time of imaging. Ann Nucl Med. 2012;26(6):501–7.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Rowe SP, Gorin MA, Allaf ME, et al. PET imaging of prostate-specific membrane antigen in prostate cancer: current state of the art and future challenges. Prostate Cancer Prostatic Dis. 2016;19(3):223–30.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Rauscher I, Maurer T, Fendler WP, Sommer WH, Schwaiger M, Eiber M. (68)Ga-PSMA ligand PET/CT in patients with prostate cancer: how we review and report. Cancer Imaging. 2016;16(1):14.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Perera M, Papa N, Christidis D, et al. Sensitivity, specificity, and predictors of positive 68Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70(6):926–37.CrossRefPubMedGoogle Scholar
  15. 15.
    Uprimny C, Kroiss AS, Decristoforo C, et al. 68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44(6):941–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Weineisen M, Simecek J, Schottelius M, Schwaiger M, Wester HJ. Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. EJNMMI Res. 2014;4(1):63.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Eder M, Schafer M, Bauder-Wust U, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23(4):688–97.CrossRefPubMedGoogle Scholar
  18. 18.
    Banerjee SR, Pullambhatla M, Byun Y, et al. 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer. J Med Chem. 2010;53(14):5333–41.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Fendler WP, Eiber M, Beheshti M, 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(6):1014–24.CrossRefPubMedGoogle Scholar
  20. 20.
    Afshar-Oromieh A, Sattler LP, Mier W, et al. The clinical impact of additional late PET/CT imaging with 68Ga-PSMA-11 (HBED-CC) in the diagnosis of prostate cancer. J Nucl Med. 2017;58(5):750–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Kabasakal L, Demirci E, Ocak M, et al. Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging. Nucl Med Commun. 2015;36(6):582–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Schmuck S, Nordlohne S, von Klot CA, et al. Comparison of standard and delayed imaging to improve the detection rate of [68Ga]PSMA I&T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44(6):960–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Schmuck S, Mamach M, Wilke F, et al. Multiple time-point 68Ga-PSMA I&T PET/CT for characterization of primary prostate cancer: value of early dynamic and delayed imaging. Clin Nucl Med. 2017;42(6):e286–93.CrossRefPubMedGoogle Scholar
  24. 24.
    Nielsen ME, Partin AW. The impact of definitions of failure on the interpretation of biochemical recurrence following treatment of clinically localized prostate cancer. Rev Urol. 2007;9(2):57–62.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Eder M, Neels O, Muller M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals. 2014;7(7):779–96.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sahlmann CO, Meller B, Bouter C, 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(5):898–905.CrossRefPubMedGoogle Scholar
  27. 27.
    Afshar-Oromieh A, Hetzheim H, Kubler W, 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(9):1611–20.CrossRefPubMedGoogle Scholar
  28. 28.
    Lutje S, Blex S, Gomez B, et al. Optimization of acquisition time of 68Ga-PSMA-ligand PET/MRI in patients with local and metastatic prostate cancer. PLoS One. 2016;11(10):e0164392.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Mohsen Beheshti
    • 1
    • 2
  • Zeinab Paymani
    • 1
    • 3
  • Joana Brilhante
    • 4
  • Hans Geinitz
    • 5
  • Daniela Gehring
    • 1
  • Thomas Leopoldseder
    • 1
  • Ludovic Wouters
    • 4
  • Christian Pirich
    • 2
  • Wolfgang Loidl
    • 6
  • Werner Langsteger
    • 1
  1. 1.Department of Nuclear Medicine & EndocrinologyPET-CT Center LINZ, Ordensklinikum, St. Vincent’s HospitalLinzAustria
  2. 2.Department of Nuclear Medicine & EndocrinologyParacelsus Medical UniversitySalzburgAustria
  3. 3.Research Center for Nuclear MedicineShariati Hospital, Tehran University of Medical SciencesTehranIran
  4. 4.Department of Radiation OncologyOrdensklinikum, St. Vincent’s HospitalLinzAustria
  5. 5.ANMI SALiegeBelgium
  6. 6.Department of UrologyProstate Cancer Center, Ordensklinikum, St. Vincent’s HospitalLinzAustria

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