Download PDF
Aktuelle Urol 2017; 48(02): 140-147
DOI: 10.1055/s-0043-100269
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Bedeutung und Nutzen von PSMA-Liganden beim Prostatakarzinom

Significance and Value of PSMA Ligands in Prostate Cancer
Claudia Gasch
1   Urologische Klinik, Universitätsklinikum Heidelberg, Heidelberg
,
Stefan Körber
2   Abteilung Radioonkologie und Strahlentherapie, Radiologische Klinik, Universitätsklinikum Heidelberg, Heidelberg
,
Christophe Kremer
3   Abteilung Nuklearmedizin, Radiologische Klinik, Universitätsklinikum Heidelberg, Heidelberg
,
Matthias Eiber
4   Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München
,
Clemens Kratochwil
3   Abteilung Nuklearmedizin, Radiologische Klinik, Universitätsklinikum Heidelberg, Heidelberg
,
Uwe Haberkorn
3   Abteilung Nuklearmedizin, Radiologische Klinik, Universitätsklinikum Heidelberg, Heidelberg
,
Markus Hohenfellner
1   Urologische Klinik, Universitätsklinikum Heidelberg, Heidelberg
,
Boris Hadaschik
1   Urologische Klinik, Universitätsklinikum Heidelberg, Heidelberg
,
Frederik L. Giesel
3   Abteilung Nuklearmedizin, Radiologische Klinik, Universitätsklinikum Heidelberg, Heidelberg
› Author Affiliations
Further Information

Publication History

Publication Date:
16 May 2017 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Über die letzten Jahre haben PSMA-Liganden in der PET-Diagnostik, wie der Tracer 68Ga-PSMA-11, vielversprechende Ergebnisse gezeigt und so zur Verbesserung der Versorgung von Prostatakarzinompatienten beigetragen. Den häufigsten Einsatz in der bildgebenden Diagnostik hat z. Z. der Tracer 68Ga-PSMA-11 im biochemischen Rezidiv des Prostatakarzinoms. Hier zeigt die 68Ga-PSMA-11 PET/CT im Vergleich zu konventionellen Bildgebungsmodalitäten hervorragende Detektionsraten. Insbesondere kleine, morphologisch unauffällige Läsionen sowie Läsionen bei geringen PSA-Werten können besser detektiert werden. Auch im primären Staging von High risk-Patienten, vor allem in Kombination mit der multiparametrischen MRT, stellt die 68Ga-PSMA PET eine aussichtsvolle Alternative dar. Neben der wachsenden Anwendung in der Diagnostik, werden verschiedene PSMA-Liganden auch bereits im therapeutischen Bereich erfolgreich eingesetzt. Therapierefraktäre metastasierte Prostatakarzinompatienten zeigten ein gutes Ansprechen auf die PSMA-Radioligandentherapie mit kontrollierbaren Nebenwirkungen.

Aufgrund der aktuellen Entwicklungen werden PSMA-Liganden beim Management von Prostatakarzinompatienten weiterhin eine wichtige Rolle einnehmen und ihr Einsatz eine verbreiterte Anwendung finden.

Abstract

In recent years, PSMA-targeting PET tracers such as 68Ga-PSMA-11 have shown promising results, thus contributing to a better management of prostate cancer patients. At the present time, 68Ga-PSMA-11 is most frequently used for diagnostic evaluation in the setting of biochemical recurrence of prostate cancer. In this context, the 68Ga-PSMA-11 PET/CT delivers superior detection rates compared to conventional imaging, especially for the detection of small, unsuspicious lesions or lesions in the presence of low PSA values. Furthermore, 68Ga-PSMA PET imaging seems to be an encouraging alternative for the staging of high-risk patients, particularly in combination with multiparametric MRI. In addition to the increasing use of PSMA ligands in clinical diagnostics, some variants have also been successfully applied in therapy. Advanced metastasized prostate cancer patients showed a good response to PSMA radioligand therapy with tolerable side-effects after failure of guideline-compliant treatment.

Due to recent developments, PSMA ligands will continue to play an important role in the management of prostate cancer patients and will be more widely used in the future.

Schlüsselwörter

Prostatakarzinom - PSMA - PET - Staging - Radioligandentherapie

Key words

prostate cancer - PSMA - PET - staging - radioligand therapy
 

  • Literatur

  • 1 Torre LA, Bray F, Siegel RL. et al. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108 doi: 10.3322/caac.21262
    CrossrefPubMedGoogle Scholar
  • 2 Lozano R, Naghavi M, Foreman K. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet (London, England) 2012; 380: 2095-2128 10.1016/S0140-6736(12)61728-0
    CrossrefPubMedGoogle Scholar
  • 3 Mottet N, Bellmunt J, Bolla M. et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2016; DOI: 10.1016/j.eururo.2016.08.003.
    CrossrefPubMedGoogle Scholar
  • 4 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft - Deutsche Krebshilfe – AWMF): Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, 2014 AWMF Registernummer: 034/022 OL.http://leitlinienprogramm Onkologie.de/Leitlinien.7.0.html (Zugriff am 27.09.16)
    PubMed
  • 5 Yu CY, Desai B, Ji L. et al. Comparative performance of PET tracers in biochemical recurrence of prostate cancer: A critical analysis of literature. Am J Nucl Med Mol Imaging 2014; 4: 580-601
    PubMedGoogle Scholar
  • 6 Evangelista L, Guttilla A, Zattoni F. et al. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Eur Urol 2013; 63: 1040-1048, 10.1016/j.eururo.2012.09.039
    CrossrefPubMedGoogle Scholar
  • 7 Jadvar H. Imaging evaluation of prostate cancer with 18F-fluorodeoxyglucose PET/CT: Utility and limitations. Eur J Nucl Med Mol Imaging 2013; 40 (Suppl. 01) S5-S10 10.1007/s00259-013-2361-7
    CrossrefPubMedGoogle Scholar
  • 8 Schoder H. 2-[18F]Fluoro-2-Deoxyglucose positron emission tomography for the detection of disease in patients with prostate-specific antigen relapse after radical prostatectomy. Clin Cancer Res 2005; 11: 4761-4769 10.1158/1078-0432.CCR-05-0249
    CrossrefPubMedGoogle Scholar
  • 9 Murphy GP, Elgamal A-AA, Su SL. et al. Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen. Cancer 1998; 83: 2259-2269 10.1002/(SICI)1097-0142(19981201)83:11<2259::AID-CNCR5>3.0.CO;2-T
    CrossrefPubMedGoogle Scholar
  • 10 Bostwick DG, Pacelli A, Blute M. et al. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: A study of 184 cases. Cancer 1998; 82: 2256-2261
    CrossrefPubMedGoogle Scholar
  • 11 Silver DA, Pellicer I, Fair WR. et al. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997; 3: 81-85
    PubMedGoogle Scholar
  • 12 Afshar-Oromieh A, Haberkorn U, Eder M. et al. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: Comparison with 18F-FECH. Eur J Nucl Med Mol Imaging 2012; 39: 1085-1086 10.1007/s00259-012-2069-0
    CrossrefPubMedGoogle Scholar
  • 13 Rajasekaran SA, Anilkumar G, Oshima E. et al. A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. Mol Biol Cell 2003; 14: 4835-4845 10.1091/mbc.E02-11-0731
    CrossrefPubMedGoogle Scholar
  • 14 Cornford P, Bellmunt J, Bolla M et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol 2016, doi:10.1016/j.eururo.2016.08.002
    PubMed
  • 15 de Rooij M, Hamoen EHJ, Witjes JA. et al. Accuracy of magnetic resonance imaging for local staging of prostate cancer: a diagnostic meta-analysis. Eur Urol 2016; 70: 233-245 10.1016/j.eururo.2015.07.029
    CrossrefPubMedGoogle Scholar
  • 16 Kelloff GJ, Choyke P, Coffey DS. Challenges in clinical prostate cancer: role of imaging. Am J Roentgenol 2009; 192: 1455-1470 10.2214/AJR.09.2579
    CrossrefPubMedGoogle Scholar
  • 17 Rajinikanth A, Manoharan M, Soloway CT. et al. Trends in Gleason score: Concordance between biopsy and prostatectomy over 15 years. Urology 2008; 72: 177-182 10.1016/j.urology.2007.10.022
    CrossrefPubMedGoogle Scholar
  • 18 Valerio M, Donaldson I, Emberton M. et al. Detection of clinically significant prostate cancer using magnetic resonance imaging-ultrasound fusion targeted biopsy: A systematic review. Eur Urol 2015; 68: 8-19 10.1016/j.eururo.2014.10.026
    CrossrefPubMedGoogle Scholar
  • 19 Eiber M, Weirich G, Holzapfel K. et al. Simultaneous (68)Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol 2016; DOI: 10.1016/j.eururo.2015.12.053.
    CrossrefPubMedGoogle Scholar
  • 20 Giesel FL, Sterzing F, Schlemmer HP. et al. Intra-individual comparison of (68)Ga-PSMA-11-PET/CT and multi-parametric MR for imaging of primary prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 1400-1406 10.1007/s00259-016-3346-0
    CrossrefPubMedGoogle Scholar
  • 21 Pfister D, Bolla M, Briganti A. et al. Early salvage radiotherapy following radical prostatectomy. Eur Urol 2014; 65: 1034-1043 10.1016/j.eururo.2013.08.013
    CrossrefPubMedGoogle Scholar
  • 22 Rouvière O, Vitry T, Lyonnet D. Imaging of prostate cancer local recurrences: Why and how?. Eur Radiol 2010; 20: 1254-1266 10.1007/s00330-009-1647-4
    CrossrefPubMedGoogle Scholar
  • 23 Afshar-Oromieh A, Avtzi E, Giesel FL. et al. The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015; 42: 197-209 10.1007/s00259-014-2949-6
    CrossrefPubMedGoogle Scholar
  • 24 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: 668-674 10.2967/jnumed.115.154153
    CrossrefPubMedGoogle Scholar
  • 25 Morigi JJ, Stricker PD, van Leeuwen PJ. et al. Prospective comparison of 18F-Fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising psa after curative treatment and are being considered for targeted therapy. J Nucl Med 2015; 56: 1185-1190 10.2967/jnumed.115.160382
    CrossrefPubMedGoogle Scholar
  • 26 Afshar-Oromieh A, Zechmann CM, Malcher A. 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 10.1007/s00259-013-2525-5
    CrossrefPubMedGoogle Scholar
  • 27 Krause BJ, Souvatzoglou M, Tuncel M. et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging 2008; 35: 18-23 10.1007/s00259-007-0581-4
    CrossrefPubMedGoogle Scholar
  • 28 van Leeuwen PJ, Stricker P, Hruby G. et al. 68 Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int 2016; 117: 732-739 10.1111/bju.13397
    CrossrefPubMedGoogle Scholar
  • 29 Ceci F, Uprimny C, Nilica B. et al. 68Ga-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: 1284-1294 10.1007/s00259-015-3078-6
    CrossrefPubMedGoogle Scholar
  • 30 Perera M, Papa N, Christidis D. 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; DOI: 10.1016/j.eururo.2016.06.021.
    CrossrefPubMedGoogle Scholar
  • 31 Pyka T, Okamoto S, Dahlbender M. et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 2114-2121 10.1007/s00259-016-3435-0
    CrossrefPubMedGoogle Scholar
  • 32 D’Amico AV, Moul J, Carroll PR. et al. Cancer-specific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era. J Clin Oncol 2003; 21: 2163-2172 10.1200/JCO.2003.01.075
    CrossrefPubMedGoogle Scholar
  • 33 Eifler JB, Feng Z, Lin BM. et al. An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011. BJU Int 2013; 111: 22-29 10.1111/j.1464-410X.2012.11324.x
    CrossrefPubMedGoogle Scholar
  • 34 Zamboglou C, Schiller F, Fechter T. et al. (68)Ga-HBED-CC-PSMA PET/CT versus histopathology in primary localized prostate cancer: A voxel-wise comparison. Theranostics 2016; 6: 1619-1628 10.7150/thno.15344
    CrossrefPubMedGoogle Scholar
  • 35 Hövels AM, Heesakkers RAM, Adang EM. et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: A meta-analysis. Clin Radiol 2008; 63: 387-395 10.1016/j.crad.2007.05.022
    CrossrefPubMedGoogle Scholar
  • 36 Maurer T, Gschwend JE, Rauscher I. et al. Diagnostic efficacy of 68Gallium-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: 1436-1443 10.1016/j.juro.2015.12.025
    CrossrefPubMedGoogle Scholar
  • 37 Dewes S, Schiller K, Sauter K. et al. Integration of 68Ga-PSMA-PET imaging in planning of primary definitive radiotherapy in prostate cancer: A retrospective study. Radiat Oncol 2016; 11: 73 10.1186/s13014-016-0646-2
    CrossrefPubMedGoogle Scholar
  • 38 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: 34-41 10.1007/s00259-015-3188-1
    CrossrefPubMedGoogle Scholar
  • 39 Kasperzyk JL, Finn SP. Flavin R et al. Prostate-specific membrane antigen protein expression in tumor tissue and risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev 2013; 22: 2354-2363 10.1158/1055-9965.EPI-13-0668
    CrossrefPubMedGoogle Scholar
  • 40 von Eyben FE, Kiljunen T, Kangasmaki A. et al. Radiotherapy boost for the dominant intraprostatic cancer lesion – A systematic review and meta-analysis. Clin Genitourin Cancer 2016; 14: 189-197 10.1016/j.clgc.2015.12.005
    CrossrefPubMedGoogle Scholar
  • 41 Bhardwaj H, Stephens M, Bhatt M. et al. Prostate-specific membrane antigen pet/ct findings for hepatic hemangioma. Clin Nucl Med 2016; 41: 968-969 10.1097/RLU.0000000000001384
    CrossrefPubMedGoogle Scholar
  • 42 Hermann RM, Djannatian M, Czech N. et al. Prostate-specific membrane antigen PET/CT: False-positive results due to sarcoidosis?. Case Rep Oncol 2016; 9: 457-463 10.1159/000447688
    CrossrefPubMedGoogle Scholar
  • 43 Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur Urol 2007; 52: 29-37 10.1016/j.eururo.2007.04.020
    CrossrefPubMedGoogle Scholar
  • 44 Herlemann A, Wenter V, Kretschmer A. et al. 68Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol 2016; 70: 553-557 10.1016/j.eururo.2015.12.051
    CrossrefPubMedGoogle Scholar
  • 45 Budäus L, Leyh-Bannurah S-R, Salomon G. et al. Initial experience of 68Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol 2016; 69: 393-396 10.1016/j.eururo.2015.06.010
    CrossrefPubMedGoogle Scholar
  • 46 Vinsensia M, Chyoke P, Hadaschik B et al. 68Ga-PSMA PET/CT and volumetric morphology of PET-positive lymph nodes stratified by tumor differentiation of prostate cancer. JNM 2017 [in press]
    PubMed
  • 47 Giesel FL, Fiedler H, Stefanova M. et al. PSMA PET/CT with Glu-urea-Lys-(Ahx)-[68Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015; 42: 1794-1800 10.1007/s00259-015-3106-6
    CrossrefPubMedGoogle Scholar
  • 48 Rauscher I, Düwel C, Wirtz M. et al. Value of (111) In-PSMA-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: Correlation with histopathology and clinical follow-up. BJU Int 2016; DOI: 10.1111/bju.13713.
    CrossrefPubMedGoogle Scholar
  • 49 Robu S, Schottelius M, Eiber M. et al. Preclinical evaluation and first patient application of 99mTc-PSMA-I&S for SPECT imaging and radioguided surgery in prostate cancer. J Nucl Med 2016; DOI: : 10.2967/jnumed.116.178939.
    CrossrefPubMedGoogle Scholar
  • 50 Delker A, Fendler WP, Kratochwil C. et al. Dosimetry for 177Lu-DKFZ-PSMA-617: A new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 42-51 10.1007/s00259-015-3174-7
    CrossrefPubMedGoogle Scholar
  • 51 Kratochwil C, Giesel FL, Stefanova M. et al. PSMA-Targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med 2016; 57: 1170-1176 10.2967/jnumed.115.171397
    CrossrefPubMedGoogle Scholar
  • 52 Ahmadzadehfar H, Eppard E, Kürpig S. et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget 2016; 7: 12477-12488 10.18632/oncotarget.7245
    CrossrefPubMedGoogle Scholar
  • 53 Rahbar K, Ahmadzadehfar H, Kratochwil C. et al. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. J Nucl Med 2016; DOI: 10.2967/jnumed.116.183194.
    CrossrefPubMedGoogle Scholar
  • 54 Kratochwil C, Bruchertseifer F, Giesel FL. et al. 225Ac-PSMA-617 for PSMA targeting alpha-radiation therapy of patients with metastatic castration-resistant prostate cancer. J Nucl Med 2016; DOI: 10.2967/jnumed.116.178673.
    CrossrefPubMedGoogle Scholar
  • 55 Giesel FL, Hadaschik B, Cardinale J. et al. F-18 labelled PSMA-1007: Biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J Nucl Med Mol Imaging 2016; 44: 678 10.1007/s00259-016-3573-4
    PubMedGoogle Scholar
  • 56 Giesel FL, Kesch C, Yun M. et al. 18F-PSMA-1007 PET/CT Detects Micrometastases in a Patient With Biochemically Recurrent Prostate Cancer. Clin Genitourin Cancer 2016 DOI: 10.1016/j.clgc.2016.12.029.
    CrossrefPubMedGoogle Scholar