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Combined Early and Late [68Ga]PSMA-HBED-CC PET Scans Improve Lesion Detectability in Biochemical Recurrence of Prostate Cancer with Low PSA Levels

  • M. Hohberg
  • C. Kobe
  • P. Täger
  • J. Hammes
  • M. Schmidt
  • F. Dietlein
  • M. Wild
  • A. Heidenreich
  • A. Drzezga
  • M. Dietlein
Research Article
  • 125 Downloads

Abstract

Purpose

Our aim was to evaluate the benefit of early (1 h post-injection (p.i.)) and late (3 h p.i.) [68Ga]PSMA-HBED-CC positron emission tomography (PET)/x-ray computed tomography (CT) imaging for detection of biochemical recurrence (BCR) of prostate cancer (PCa).

Procedures

Seventy patients with BCR of the PCa and prostate-specific antigen (PSA) levels of less than 2.0 μg/l were subjected to [68Ga]PSMA-HBED-CC PET (mean injected activity 180 MBq). While early imaging contained whole body scans, late imaging was confined to the pelvis and the lower abdomen. Uptake in suspicious lesions was analyzed by peak and maximum standardized uptake values (SUVpeak/max). Tumor-to-background ratios were calculated for all lesions in which the liver served as reference organ. The Wilcoxon matched-pair signed-rank test was used to compare the uptake in suspicious lesions between early and late imaging. Follow-up data were used to validate the existence of the additionally detected lesions.

Results

Forty-four of the 70 patients thus examined were interpreted as PSMA-positive in early and/or late scans while 26 remained without suspicion of PSMA tracer uptake. A total of 70 suspicious lesions were analyzed. Ten tumor-suspicious lesions from seven different patients were better or exclusively visible in the late measurements while three tumor-suspicious lesions from three different patients were better or exclusively visible in the early images. A validation by follow-up data was possible for 11 of these 13 additionally detected lesions. In direct comparison between early and late imaging, the mean SUVmax in PSMA-positive lesions was 74 % higher (p < 0.001) and the mean SUVpeak was 36 % higher (p = 0.001) in the late scans. The SUVmean in the reference regions was decreasing in the late measurements, whereas the mean TBR increased by a factor of 3 (p < 0.001). Taking confirmed lesions only into account, we estimated a 10 % gain in additionally detected PSMA-positive lesions (7/70) within the patient cohort.

Conclusions

The time period between injection and data acquisition influences the detection rate of [68Ga]PSMA-HBED-CC PET/CT. In biochemical recurrence with low PSA levels, late [68Ga]PSMA-HBED-CC PET/CT imaging offers frequent advantages with regard to lesion contrast.

Key words

[68Ga]PSMA-HBED-CC PET Early and late scans Lesion detectability PSMA 

Notes

Compliance with Ethical Standards

This analysis was conducted in accordance with the Institutional Review Board (IRB). All patients gave written informed consent to PET imaging and inclusion of their data in a retrospective analysis. All procedures were performed in compliance with the regulations of the local authorities responsible (District Administration of Cologne, Germany).

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Cornford P, Bellmunt J, Bolla M, Briers E, de Santis M, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, van der Poel HG, van der Kwast TH, Rouvière O, Wiegel T, Mottet N (2017) EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol 71:630–642CrossRefPubMedGoogle Scholar
  2. 2.
    Hillier SM, Maresca KP, Femia FJ, Marquis JC, Foss CA, Nguyen N, Zimmerman CN, Barrett JA, Eckelman WC, Pomper MG, Joyal JL, Babich JW (2009) Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res 69:6932–6940CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Eder M, Schäfer M, Bauder-Wüst U, Hull WE, Wängler C, Mier W, Haberkorn U, Eisenhut M (2012) Ga-68-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 23:688–697CrossRefPubMedGoogle Scholar
  4. 4.
    Schäfer M, Bauder-Wüst U, Leotta K, Zoller F, Mier W, Haberkorn U, Eisenhut M, Eder M (2012) A dimerized urea-based inhibitor of the prostate-specific membrane antigen for Ga-68-PET imaging of prostate cancer. EJNMMI Res 2:23CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bander NH (2006) Technology insight: monoclonal antibody imaging of prostate cancer. Nat Clin Pract Urol 3:216–225CrossRefPubMedGoogle Scholar
  6. 6.
    Liu H, Moy P, Kim S, Xia Y, Rajasekaran A, Navarro V, Knudsen B, Bander NH (1997) Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res 57:3629–3634PubMedGoogle Scholar
  7. 7.
    Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Graner FP, Kubler H, Haberhorn U, Eisenhut M, Wester HJ, Gschwend JE, Schwaiger M (2015) Evaluation of hybrid [68Ga]PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 56:668–674CrossRefPubMedGoogle Scholar
  8. 8.
    Rauscher S, Maurer T, Fendler WP et al (2016) [68Ga]PSMA ligand PET/CT in patients with prostate cancer: how we review and report. Cancer Imaging 16:14CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Sahlmann CO, Meller B, Bouter C, Ritter CO, Ströbel P, Lotz J, Trojan L, Meller J, Hijazi S (2016) Biphasic [68Ga]PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma. Eur J Nucl Med Mol Imaging 43:898–905CrossRefPubMedGoogle Scholar
  10. 10.
    Rahbar K, Vehren T, Boegemann M et al (2015) Dual time point PET/CT acquisition using Ga-68-PSMA-Radioligand. J Nucl Med 56(supplement 3):1437Google Scholar
  11. 11.
    Afshar-Oromieh A, Sattler LP, Mier W, Hadaschik BA, Debus J, Holland-Letz T, Kopka K, Haberkorn U (2017) The clinical impact of additional late PET/CT imaging with [68Ga]PSMA-11 (HBED-CC) in the diagnosis of prostate cancer. J Nucl Med 58:750–755CrossRefPubMedGoogle Scholar
  12. 12.
    Derlin T, Weiberg D, von Klot C, Wester HJ, Henkenberens C, Ross TL, Christiansen H, Merseburger AS, Bengel FM (2016) [68Ga]PSMA I&T PET/CT for assessment of prostate cancer: evaluation of image quality after forced diuresis and delayed imaging. Eur Radiol 26:4345–4353CrossRefPubMedGoogle Scholar
  13. 13.
    Schmuck S, Nordlohne S, von Klot CA, Henkenberens C, Sohns JM, Christiansen H, Wester HJ, Ross TL, Bengel FM, Derlin T (2017) 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 44:960–968CrossRefPubMedGoogle Scholar
  14. 14.
    Rowe SP, Macura KJ, Mena E, Blackford AL, Nadal R, Antonarakis ES, Eisenberger M, Carducci M, Fan H, Dannals RF, Chen Y, Mease RC, Szabo Z, Pomper MG, Cho SY (2016) PSMA-based [18F]DCFPyL PET/CT is superior to conventional imaging for lesion detection in patients with metastatic prostate Cancer. Mol Imaging Biol 18:411–419CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Wondergem M, van der Zant FM, Knol RJJ, Lazarenko SV, Pruim J, de Jong IJ (2017) 18F-DCFPyL PET/CT in the detection of prostate cancer at 60 and 120 minutes: detection rate, image quality, activity kinetics, and biodistribution. J Nucl Med 58:1797–1809CrossRefPubMedGoogle Scholar
  16. 16.
    Dietlein F, Kobe C, Neubauer S, Schmidt M, Stockter S, Fischer T, Schomäcker K, Heidenreich A, Zlatopolskiy BD, Neumaier B, Drzezga A, Dietlein M (2017) PSA-stratified performance of F-18 and Ga-68-PSMA PET in patients with biochemical relapse of prostate cancer. J Nucl Med 58:947–952CrossRefPubMedGoogle Scholar
  17. 17.
    Yan J, Schaefferkoetter J, Conti M, Townsend D (2016) A method to assess image quality for low-dose PET: analysis of SNR, CNR, bias and image noise. Cancer Imaging 16:26CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Afshar-Oromieh A, Hetzheim H, Kübler K et al (2016) Radiation dosimetry of [68Ga]PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing. Eur J Nucl Med Mol Imaging 43:1611–1620CrossRefPubMedGoogle Scholar
  19. 19.
    Hope TA, Aggarwal R, Chee B et al (2018) Impact of [68Ga]PSMA-11 PET on management in patients with biochemically recurrent prostate cancer. J Nucl Med 58:1956–1961CrossRefGoogle Scholar
  20. 20.
    Dietlein M, Kobe C, Kuhnert G, Stockter S, Fischer T, Schomäcker K, Schmidt M, Dietlein F, Zlatopolskiy BD, Krapf P, Richarz R, Neubauer S, Drzezga A, Neumaier B (2015) Comparison of [18F]DCFPyL and [68Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol 17:575–584CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Szabo Z, Mena E, Rowe SP, Plyku D, Nidal R, Eisenberger MA, Antonarakis ES, Fan H, Dannals RF, Chen Y, Mease RC, Vranesic M, Bhatnagar A, Sgouros G, Cho SY, Pomper MG (2015) Initial evaluation of [18F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol 17:565–574CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Uprimny C, Kroiss AS, Fritz J, Decristoforo C, Kendler D, von Guggenberg E, Nilica B, Maffey-Steffan J, di Santo G, Bektic J, Horninger W, Virgolini IJ (2017) Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence. Eur J Nucl Med Mol Imaging 44:1647–1655CrossRefPubMedGoogle Scholar

Copyright information

© World Molecular Imaging Society 2018

Authors and Affiliations

  1. 1.Department of Nuclear MedicineUniversity Hospital of CologneCologneGermany
  2. 2.Cancer Center CologneUniversity Hospital of CologneCologneGermany
  3. 3.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  4. 4.Department of UrologyUniversity Hospital of CologneCologneGermany

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