MRI versus 68Ga-PSMA PET/CT for gross tumour volume delineation in radiation treatment planning of primary prostate cancer

  • Constantinos Zamboglou
  • Gesche Wieser
  • Steffen Hennies
  • Irene Rempel
  • Simon Kirste
  • Martin Soschynski
  • Hans Christian Rischke
  • Tobias Fechter
  • Cordula A. Jilg
  • Mathias Langer
  • Philipp T. Meyer
  • Michael Bock
  • Anca-Ligia Grosu
Original Article



Multiparametric magnetic resonance imaging (mpMRI) is widely used in radiation treatment planning of primary prostate cancer (PCA). Focal dose escalation to the dominant intraprostatic lesions (DIPL) may lead to improved PCA control. Prostate-specific membrane antigen (PSMA) is overexpressed in most PCAs. 68Ga-labelled PSMA inhibitors have demonstrated promising results in detection of PCA with PET/CT. The aim of this study was to compare 68Ga-PSMA PET/CT with MRI for gross tumour volume (GTV) definition in primary PCA.


This retrospective study included 22 patients with primary PCA analysed after 68Ga-PSMA PET/CT and mpMRI. GTVs were delineated on MR images by two radiologists (GTV-MRIrad) and two radiation oncologists separately. Both volumes were merged leading to GTV-MRIint. GTVs based on PET/CT were delineated by two nuclear medicine physicians in consensus (GTV-PET). Laterality (left, right, and left and right prostate lobes) on mpMRI, PET/CT and pathological analysis after biopsy were assessed.


Mean GTV-MRIrad, GTV-MRIint and GTV-PET were 5.92, 3.83 and 11.41 cm3, respectively. GTV-PET was significant larger then GTV-MRIint (p = 0.003). The MRI GTVs GTV-MRIrad and GTV-MRIint showed, respectively, 40 % and 57 % overlap with GTV-PET. GTV-MRIrad and GTV-MRIint included the SUVmax of GTV-PET in 12 and 11 patients (54.6 % and 50 %), respectively. In nine patients (47 %), laterality on mpMRI, PET/CT and histopathology after biopsy was similar.


Ga-PSMA PET/CT and mpMRI provided concordant results for delineation of the DIPL in 47 % of patients (40 % – 54 % of lesions). GTV-PET was significantly larger than GTV-MRIint. 68Ga-PSMA PET/CT may have a role in radiation treatment planning for focal radiation to the DIPL. Exact correlation of PET and MRI images with histopathology is needed.


PSMA Prostate cancer MRI Radiation therapy 


  1. 1.
    Bott SR, Ahmed HU, Hindley RG, Abdul-Rahman A, Freeman A, Emberton M. The index lesion and focal therapy: an analysis of the pathological characteristics of prostate cancer. BJU Int. 2010;106:1607–11. doi:10.1111/j.1464-410X.2010.09436.x.CrossRefPubMedGoogle Scholar
  2. 2.
    Arrayeh E, Westphalen AC, Kurhanewicz J, Roach 3rd M, Jung AJ, Carroll PR, et al. Does local recurrence of prostate cancer after radiation therapy occur at the site of primary tumor? Results of a longitudinal MRI and MRSI study. Int J Radiat Oncol Biol Phys. 2012;82:e787–93. doi:10.1016/j.ijrobp.2011.11.030.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Niyazi M, Bartenstein P, Belka C, Ganswindt U. Choline PET based dose-painting in prostate cancer—modelling of dose effects. Radiat Oncol. 2010;5:23. doi:10.1186/1748-717X-5-23.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Fonteyne V, Villeirs G, Speleers B, De Neve W, De Wagter C, Lumen N, et al. Intensity-modulated radiotherapy as primary therapy for prostate cancer: report on acute toxicity after dose escalation with simultaneous integrated boost to intraprostatic lesion. Int J Radiat Oncol Biol Phys. 2008;72:799–807. doi:10.1016/j.ijrobp.2008.01.040.CrossRefPubMedGoogle Scholar
  5. 5.
    Pinkawa M, Piroth MD, Holy R, Klotz J, Djukic V, Corral NE, et al. Dose-escalation using intensity-modulated radiotherapy for prostate cancer – evaluation of quality of life with and without (18)F-choline PET-CT detected simultaneous integrated boost. Radiat Oncol. 2012;7:14. doi:10.1186/1748-717X-7-14.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Lips IM, van der Heide UA, Haustermans K, van Lin EN, Pos F, Franken SP, et al. Single blind randomized phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial. Trials. 2011;12:255. doi:10.1186/1745-6215-12-255.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Turkbey B, Pinto PA, Mani H, Bernardo M, Pang Y, McKinney YL, et al. Prostate cancer: value of multiparametric MR imaging at 3 T for detection--histopathologic correlation. Radiology. 2010;255:89–99. doi:10.1148/radiol.09090475.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Yakar D, Debats OA, Bomers JG, Schouten MG, Vos PC, van Lin E, et al. Predictive value of MRI in the localization, staging, volume estimation, assessment of aggressiveness, and guidance of radiotherapy and biopsies in prostate cancer. J Magn Reson Imaging. 2012;35:20–31. doi:10.1002/jmri.22790.CrossRefPubMedGoogle Scholar
  9. 9.
    Tan CH, Hobbs BP, Wei W, Kundra V. Dynamic contrast-enhanced MRI for the detection of prostate cancer: meta-analysis. AJR Am J Roentgenol. 2015;204:W439–48. doi:10.2214/AJR.14.13373.CrossRefPubMedGoogle Scholar
  10. 10.
    Kwee SA, Wei H, Sesterhenn I, Yun D, Coel MN. Localization of primary prostate cancer with dual-phase 18F-fluorocholine PET. J Nucl Med. 2006;47:262–9.PubMedGoogle Scholar
  11. 11.
    Farsad M, Schiavina R, Castellucci P, Nanni C, Corti B, Martorana G, et al. Detection and localization of prostate cancer: correlation of (11)C-choline PET/CT with histopathologic step-section analysis. J Nucl Med. 2005;46:1642–9.PubMedGoogle Scholar
  12. 12.
    Chang JH, Joon DL, Lee ST, Gong SJ, Scott AM, Davis ID, et al. Histopathological correlation of (11)C-choline PET scans for target volume definition in radical prostate radiotherapy. Radiother Oncol. 2011;99:187–92. doi:10.1016/j.radonc.2011.03.012.CrossRefPubMedGoogle Scholar
  13. 13.
    Grosu AL, Weirich G, Wendl C, Prokic V, Kirste S, Geinitz H, et al. 11C-Choline PET/pathology image coregistration in primary localized prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:2242–8. doi:10.1007/s00259-014-2861-0.CrossRefPubMedGoogle Scholar
  14. 14.
    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. 2014;7:779–96. doi:10.3390/ph7070779.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Mhawech-Fauceglia P, Zhang S, Terracciano L, Sauter G, Chadhuri A, Herrmann FR, et al. Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using multiple tumour tissue microarray technique. Histopathology. 2007;50:472–83. doi:10.1111/j.1365-2559.2007.02635.x.CrossRefPubMedGoogle Scholar
  16. 16.
    Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3:81–5.PubMedGoogle Scholar
  17. 17.
    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. doi:10.1021/bc200279b.CrossRefPubMedGoogle Scholar
  18. 18.
    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. doi:10.2967/jnumed.115.154153.CrossRefPubMedGoogle Scholar
  19. 19.
    Ceci F, Uprimny C, Nilica B, Geraldo L, Kendler D, Kroiss A, et al. Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging. 2015;42:1284–94. doi:10.1007/s00259-015-3078-6.CrossRefPubMedGoogle Scholar
  20. 20.
    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. doi:10.1007/s00259-013-2525-5.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Rowe SP, Gage KL, Faraj SF, Macura KJ, Cornish TC, Gonzalez-Roibon N, et al. 18F-DCFBC PET/CT for PSMA-based detection and characterization of primary prostate cancer. J Nucl Med. 2015;56:1003–10. doi:10.2967/jnumed.115.154336.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Singh AK, Guion P, Sears-Crouse N, Ullman K, Smith S, Albert PS, et al. Simultaneous integrated boost of biopsy proven, MRI defined dominant intra-prostatic lesions to 95 Gray with IMRT: early results of a phase I NCI study. Radiat Oncol. 2007;2:36. doi:10.1186/1748-717X-2-36.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    D’Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med. 2004;351:125–35. doi:10.1056/NEJMoa032975.CrossRefPubMedGoogle Scholar
  24. 24.
    van Lin EN, Futterer JJ, Heijmink SW, van der Vight LP, Hoffmann AL, van Kollenburg P, et al. IMRT boost dose planning on dominant intraprostatic lesions: gold marker-based three-dimensional fusion of CT with dynamic contrast-enhanced and 1H-spectroscopic MRI. Int J Radiat Oncol Biol Phys. 2006;65:291–303. doi:10.1016/j.ijrobp.2005.12.046.CrossRefPubMedGoogle Scholar
  25. 25.
    Eichler K, Hempel S, Wilby J, Myers L, Bachmann LM, Kleijnen J. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review. J Urol. 2006;175:1605–12. doi:10.1016/S0022-5347(05)00957-2.CrossRefPubMedGoogle Scholar
  26. 26.
    Milker-Zabel S, Zabel-du Bois A, Henze M, Huber P, Schulz-Ertner D, Hoess A, et al. Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOC-PET. Int J Radiat Oncol Biol Phys. 2006;65:222–7. doi:10.1016/j.ijrobp.2005.12.006.CrossRefPubMedGoogle Scholar
  27. 27.
    Shepherd T, Teras M, Beichel RR, Boellaard R, Bruynooghe M, Dicken V, et al. Comparative study with new accuracy metrics for target volume contouring in PET image guided radiation therapy. IEEE Trans Med Imaging. 2012;31:2006–24. doi:10.1109/TMI.2012.2202322.CrossRefPubMedGoogle Scholar
  28. 28.
    Nestle U, Kremp S, Schaefer-Schuler A, Sebastian-Welsch C, Hellwig D, Rube C, et al. Comparison of different methods for delineation of 18F-FDG PET-positive tissue for target volume definition in radiotherapy of patients with non-small cell lung cancer. J Nucl Med. 2005;46:1342–8.PubMedGoogle Scholar
  29. 29.
    Rischke HC, Beck T, Vach W, Wieser G, Grosu AL, Schultze-Seemann W, et al. Furosemide diminishes (18)F-fluoroethylcholine uptake in prostate cancer in vivo. Eur J Nucl Med Mol Imaging. 2014;41:2074–82. doi:10.1007/s00259-014-2829-0.CrossRefPubMedGoogle Scholar
  30. 30.
    Eiber M, Nekolla SG, Maurer T, Weirich G, Wester HJ, Schwaiger M. Ga-PSMA PET/MR with multimodality image analysis for primary prostate cancer. Abdom Imaging. 2015;40:1769–71. doi:10.1007/s00261-014-0301-z.CrossRefPubMedGoogle Scholar
  31. 31.
    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. doi:10.1007/s00259-014-2949-6.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Dietlein M, Kobe C, Kuhnert G, Stockter S, Fischer T, Schomacker K, et al. Comparison of [(18)F]DCFPyL and [(68)Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol. 2015;17:575–84. doi:10.1007/s11307-015-0866-0.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Herrmann K, Bluemel C, Weineisen M, Schottelius M, Wester HJ, Czernin J, et al. Biodistribution and radiation dosimetry for a probe targeting prostate-specific membrane antigen for imaging and therapy. J Nucl Med. 2015;56:855–61. doi:10.2967/jnumed.115.156133.CrossRefPubMedGoogle Scholar
  34. 34.
    Padhani AR, Gapinski CJ, Macvicar DA, Parker GJ, Suckling J, Revell PB, et al. Dynamic contrast enhanced MRI of prostate cancer: correlation with morphology and tumour stage, histological grade and PSA. Clin Radiol. 2000;55:99–109. doi:10.1053/crad.1999.0327.CrossRefPubMedGoogle Scholar
  35. 35.
    Oto A, Yang C, Kayhan A, Tretiakova M, Antic T, Schmid-Tannwald C, et al. Diffusion-weighted and dynamic contrast-enhanced MRI of prostate cancer: correlation of quantitative MR parameters with Gleason score and tumor angiogenesis. AJR Am J Roentgenol. 2011;197:1382–90. doi:10.2214/AJR.11.6861.CrossRefPubMedGoogle Scholar
  36. 36.
    Tamada T, Sone T, Higashi H, Jo Y, Yamamoto A, Kanki A, et al. Prostate cancer detection in patients with total serum prostate-specific antigen levels of 4–10 ng/mL: diagnostic efficacy of diffusion-weighted imaging, dynamic contrast-enhanced MRI, and T2-weighted imaging. AJR Am J Roentgenol. 2011;197:664–70. doi:10.2214/AJR.10.5923.CrossRefPubMedGoogle Scholar
  37. 37.
    Mannweiler S, Amersdorfer P, Trajanoski S, Terrett JA, King D, Mehes G. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res. 2009;15:167–72. doi:10.1007/s12253-008-9104-2.CrossRefPubMedGoogle Scholar
  38. 38.
    Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, et al. ESUR prostate MR guidelines 2012. Eur Radiol. 2012;22:746–57. doi:10.1007/s00330-011-2377-y.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Rischke HC, Nestle U, Fechter T, Doll C, Volegova-Neher N, Henne K, et al. 3 Tesla multiparametric MRI for GTV-definition of dominant intraprostatic lesions in patients with prostate cancer – an interobserver variability study. Radiat Oncol. 2013;8:183. doi:10.1186/1748-717X-8-183.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Constantinos Zamboglou
    • 1
    • 2
  • Gesche Wieser
    • 3
  • Steffen Hennies
    • 4
  • Irene Rempel
    • 5
  • Simon Kirste
    • 1
    • 2
  • Martin Soschynski
    • 5
  • Hans Christian Rischke
    • 1
  • Tobias Fechter
    • 1
    • 2
  • Cordula A. Jilg
    • 6
  • Mathias Langer
    • 5
  • Philipp T. Meyer
    • 2
    • 3
  • Michael Bock
    • 2
    • 5
  • Anca-Ligia Grosu
    • 1
    • 2
  1. 1.Department of Radiation OncologyUniversity Medical Center FreiburgFreiburgGermany
  2. 2.German Cancer Consortium (DKTK)HeidelbergGermany
  3. 3.Department of Nuclear MedicineUniversity Medical Center FreiburgFreiburgGermany
  4. 4.Department of Radiation OncologyUniversity Medical Center GöttingenGöttingenGermany
  5. 5.Department of RadiologyUniversity Medical Center FreiburgFreiburgGermany
  6. 6.Department of UrologyUniversity Medical Center FreiburgFreiburgGermany

Personalised recommendations