Skip to main content
SpringerLink
Log in

Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To investigate the value of 68Ga-HBED-CC PSMA (68Ga-PSMA) PET/CT for response assessment in metastatic castration-sensitive and castration-resistant prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy.

Methods

68Ga-PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three cycles of palliative docetaxel chemotherapy. Radiographic treatment response was evaluated separately on the 68Ga-PSMA PET and CT datasets. Changes in 68Ga-PSMA uptake (SUVmean) were assessed on a per-patient and a per-lesion basis using the PERCIST scoring system with slight modification. Treatment response was defined as absence of any PSMA uptake in all target lesions on posttreatment PET (complete response, CR) or a decrease in summed SUVmean of ≥30% (partial response, PR). The appearance of a new PET-positive lesion or an increase in summed SUVmean of ≥30% (progressive disease, PD) indicated nonresponse. A moderate change in summed SUVmean (between −30% and +30%) without a change in the number of target lesions was defined as stable disease (SD). For treatment response assessment on CT, RECIST1.1 criteria were used. Radiographic responses on 68Ga-PSMA PET [RR(PET)] and on CT [RR(CT)] were compared and correlated with biochemical response (BR). A decrease in serum PSA level of ≥50% was defined as biochemical PR.

Results

Biochemical PR was found in six of seven patients with mCSPC (86%, 95% confidence interval 42% to 99.6%). The concordance rate was higher between BR and RR(PET) than between BR and RR(CT) (6/7 vs. 3/6 patients. 68Ga-PSMA PET and CT were concordant in only three patients (50%, 12% to 88%). In mCRPC patients, biochemical PR was found in six of 16 patients (38%, 15% to 65%). Outcome prediction was concordant between BR and RR(PET) in nine of 16 patients (56%), and between BR and RR(CT) in only four of 12 patients (33%) with target lesions on CT. 68Ga-PSMA PET and CT results corresponded in seven of 12 patients (58%, 28% to 85%).

Conclusion

Our preliminary results suggest that 68Ga-PSMA PET might be a promising method for treatment response assessment in mCSPC and mCRPC. The data indicate that for different metastatic sites, the performance of 68Ga-PSMA PET in response assessment might be superior to that of the conventional CT approach and could help differentiate between progressive disease and treatment response. Because of the limited number of patients, the differences revealed in our study were not statistically significant. Thus larger and prospective studies are clearly needed and warranted to confirm the value of 68Ga-PSMA PET as an imaging biomarker for response assessment.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Siegel RL, Sahar L, Portier KM, Ward EM, Jemal A. Cancer death rates in US congressional districts. CA Cancer J Clin. 2015;65:339–44.

    Article  PubMed  Google Scholar 

  2. Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. J Urol. 2002;168:9–12.

    Article  PubMed  Google Scholar 

  3. Sridhar SS, Freedland SJ, Gleave ME, Higano C, Mulders P, Parker C, et al. Castration-resistant prostate cancer: from new pathophysiology to new treatment. Eur Urol. 2014;65:289–99.

    Article  PubMed  Google Scholar 

  4. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.

    Article  CAS  PubMed  Google Scholar 

  5. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol. 2016;34:1402–18.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cook GJ, Azad G, Padhani AR. Bone imaging in prostate cancer: the evolving roles of nuclear medicine and radiology. Clin Transl Imaging. 2016;4:439–47.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8:797–805.

    Article  PubMed  Google Scholar 

  10. Weber WA. Assessing tumor response to therapy. J Nucl Med. 2009;50(Suppl 1):1S–10S.

    Article  CAS  PubMed  Google Scholar 

  11. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–68.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Caffo O, Maines F, Donner D, Veccia A, Chierichetti F, Galligioni E. Impact of enzalutamide administration on primary prostate cancer volume: a metabolic evaluation by choline positron emission tomography in castration-resistant prostate cancer patients. Clin Genitourin Cancer. 2014;12:312–6.

    Article  PubMed  Google Scholar 

  13. Ceci F, Castellucci P, Graziani T, Schiavina R, Renzi R, Borghesi M, et al. (11)C-choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel. Eur J Nucl Med Mol Imaging. 2016;43:84–91.

    Article  CAS  PubMed  Google Scholar 

  14. De Giorgi U, Caroli P, Burgio SL, Menna C, Conteduca V, Bianchi E, et al. Early outcome prediction on 18F-fluorocholine PET/CT in metastatic castration-resistant prostate cancer patients treated with abiraterone. Oncotarget. 2014;5:12448–58.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Schwarzenböck SM, Eiber M, Kundt G, Retz M, Sakretz M, Kurth J, et al. Prospective evaluation of [11C]choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2105–13.

    Article  PubMed  Google Scholar 

  16. De Giorgi U, Caroli P, Scarpi E, Conteduca V, Burgio SL, Menna C, et al. (18)F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide. Eur J Nucl Med Mol Imaging. 2015;42:1276–83.

    Article  PubMed  Google Scholar 

  17. Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13:226–35.

    Article  CAS  PubMed  Google Scholar 

  18. Afshar-Oromieh A, Haberkorn U, Hadaschik B, Habl G, Eder M, Eisenhut M, et al. PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40:1629–30.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74.

    Article  PubMed  Google Scholar 

  21. Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. 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. 2016;195:1436–43.

    Article  PubMed  Google Scholar 

  22. Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2114–21.

    Article  CAS  PubMed  Google Scholar 

  23. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65:467–79.

    Article  CAS  PubMed  Google Scholar 

  24. Eder M, Schafer M, Bauder-Wust U, Hull WE, Wangler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23:688–97.

    Article  CAS  PubMed  Google Scholar 

  25. Martin R, Juttler S, Muller M, Wester HJ. Cationic eluate pretreatment for automated synthesis of [68Ga]CPCR4.2. Nucl Med Biol. 2014;41:84–9.

    Article  CAS  PubMed  Google Scholar 

  26. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–50S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  28. Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol. 2016;70:829–36.

    Article  CAS  PubMed  Google Scholar 

  29. Budaus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, et al. Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol. 2016;69:393–6.

    Article  PubMed  Google Scholar 

  30. Hillier SM, Kern AM, Maresca KP, Marquis JC, Eckelman WC, Joyal JL, et al. 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy. J Nucl Med. 2011;52:1087–93.

    Article  CAS  PubMed  Google Scholar 

  31. Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, et al. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34:1652–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by Deutsche Forschungsgemeinschaft (DFG) under grant agreement no. SFB 824.

Author information

Authors and Affiliations

  1. Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Anna Katharina Seitz, Sophia Luther, Matthias M. Heck, Thomas Horn, Jürgen E. Gschwend & Tobias Maurer

  2. Department of Urology and Paediatric Urology, Julius Maximilians University Medical Centre of Würzburg, Würzburg, Germany

    Anna Katharina Seitz

  3. Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Isabel Rauscher, Markus Krönke, Markus Schwaiger & Matthias Eiber

  4. Institute of Medical Informatics, Statistics and Epidemiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Bernhard Haller

  5. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, USA

    Matthias Eiber

Authors
  1. Anna Katharina Seitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Isabel Rauscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernhard Haller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Markus Krönke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sophia Luther
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matthias M. Heck
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas Horn
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jürgen E. Gschwend
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Markus Schwaiger
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Matthias Eiber
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tobias Maurer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Katharina Seitz.

Ethics declarations

Conflicts of interest

None.

Ethical approval

All reported investigations were conducted in accordance with the principles of the Declaration of Helsinki and with national regulations. The study was approved by the Ethics Committee of the Technical University Munich (permit 5665/13).

Informed consent

Written informed consent for evaluation and publication of their anonymized data was obtained from all patients

Additional information

Anna Katharina Seitz and Isabel Rauscher are joint first authors.

Electronic supplementary material

ESM 1

(DOCX 78 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Seitz, A.K., Rauscher, I., Haller, B. et al. Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy. Eur J Nucl Med Mol Imaging 45, 602–612 (2018). https://doi.org/10.1007/s00259-017-3887-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-017-3887-x

Keywords

Search

Navigation