Download PDF
Der Nuklearmediziner 2014; 37(01): 38-44
DOI: 10.1055/s-0034-1370929
Zukünftige Indikationen der PET/CT
© Georg Thieme Verlag KG Stuttgart · New York

Ga-68-PSMA-PET/CT bei Prostatakarzinom

Ga-68-PSMA PET/CT for Prostate Cancer
D. Hellwig
1   Klinik für Nuklearmedizin, Universitätsklinikum des Saarlandes, Homburg
,
J. Moosbauer
2   Abteilung Nuklearmedizin, Universitätsklinikum Regensburg
,
C. Eilles
2   Abteilung Nuklearmedizin, Universitätsklinikum Regensburg
› Author Affiliations
Further Information

Publication History

Publication Date:
31 March 2014 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Prostata-spezifisches Membran-Antigen (PSMA) wird als Zelloberflächenprotein physiologisch in der Prostata exprimiert und kommt bei Prostatakarzinomen in allen Stadien vor. Auch bei kastrationsresistenten Prostatakarzinomen tritt diese Überexpression von PSMA auf. Wegen der Enzym­aktivität von PSMA konnte man spezifische Inhibitoren entwickeln, von denen sich „Small Molecule“-Radiopharmaka ableiten. Durch Kopplung des spezifisch bindenden Motives Glutamat-Harnstoff-Lysin mit dem Chelator HBED-CC, der sehr effektiv Ga-68 komplexiert, steht ein neues Radiopharmakon für die Ga-68-PSMA-PET/CT zur Verfügung. Diese neue Untersuchungsmethode weist nach den ersten Ergebnissen bei Patienten mit Prostatakarzinomen bezüglich der Bildqualität Vorteile gegenüber der Cholin-PET/CT auf. Eine erste Studie zeigte ein kontrastreicheres PET-Signal und höhere diagnostische Treffsicherheit. Die Eigenschaften auch weiterer neuer PSMA-PET-Radiopharmaka lassen eine zunehmende Bedeutung für die Diagnostik in allen Stadien des Prostatakarzinoms erwarten. In Verbindung mit PSMA-Therapie-Radiopharmaka eröffnet sich ein neues Feld der Theragnostik.

Abstract

Prostate-specific membrane antigen (PSMA) is expressed as a cell surface protein physiologically in the prostate and can be found in all stages of prostate cancer. Even in castration-resistant prostate cancers, this overexpression of PSMA occurs. Due to the enzymatic activity of PSMA it was possible develop specific inhibitors from which “small molecule” radiopharmaceuticals were derived. By coupling the specific binding motif glutamate-urea-lysine with the chelator HBED-CC, which complexes Ga-68 very effectively, a new radiopharmaceutical is available for Ga-68-PSMA-PET/CT. According to the first results in patients with prostate carcinoma, this new diagnostic tool exhibited advantages in image quality compared to choline-PET/CT. An initial study demonstrated the higher contrast of the PET signal and an improved diagnostic accuracy. The properties of even further new PSMA PET radiopharmaceuticals can be of increasing importance for the diagnostic work-up of prostate cancer in all stages.

In conjunction with therapeutic PSMA radiopharmaceuticals, a new field of theragnostics is opened.

Schlüsselwörter

PSMA - Prostatakarzinom - PET/CT - Ga-68-Glu-NH-CO-NH-Lys(Ahx)-HBED-CC

Key words

PSMA - prostate cancer - PET/CT - Ga-68-Glu-NH-CO-NH-Lys(Ahx)-HBED-CC
 

  • Literatur

  • 1 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
    CrossrefPubMedGoogle Scholar
  • 2 Afshar-Oromieh A, Malcher A, Eder M et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 2013; 40: 486-495
    CrossrefPubMedGoogle Scholar
  • 3 Afshar-Oromieh A, Zechmann CM, Malcher A et al. Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2014; 41: 11-20
    CrossrefPubMedGoogle Scholar
  • 4 Bander NH, Milowsky MI, Nanus DM et al. Phase I trial of 177Lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. Journal of Clinical Oncology 2005; 23: 4591-4601
    CrossrefPubMedGoogle Scholar
  • 5 Bauman G, Belhocine T, Kovacs M et al. 18 F-fluorocholine for prostate cancer imaging: A systematic review of the literature. Prostate Cancer and Prostatic Diseases 2012; 15: 45-55
    CrossrefPubMedGoogle Scholar
  • 6 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: 833-840
    CrossrefPubMedGoogle Scholar
  • 7 Beheshti M, Langsteger W, Sommerhuber A et al. BAY 1075553 in staging and re-staging of prostate cancer patients – Phase I study and comparison to 18F-FCH. J Nucl Med 2012; 53 (Suppl. 01) 272
    PubMedGoogle Scholar
  • 8 Chang SS, O’Keefe DS, Bacich DJ et al. Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clinical Cancer Research 1999; 5: 2674-2681
    PubMedGoogle Scholar
  • 9 Chang SS, Reuter VE, Heston WD et al. Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen. Urology 2001; 57: 801-805
    CrossrefPubMedGoogle Scholar
  • 10 Cho SY, Gage KL, Mease RC et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med 2012; 53: 1883-1891
    CrossrefPubMedGoogle Scholar
  • 11 Davis MI, Bennett MJ, Thomas LM et al. Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. Proceedings of the National Academy of Sciences of the United States of America 2005; 102: 981-986
    PubMedGoogle Scholar
  • 12 De Angelis R, Sant M, Coleman MP et al. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5-a population-based study. Lancet Oncol 2014; 15: 23-34
    CrossrefPubMedGoogle Scholar
  • 13 Eder M, Eisenhut M, Babich J et al. PSMA as a target for radiolabelled small molecules. Eur J Nucl Med Mol Imaging 2013; 40: 819-823
    CrossrefPubMedGoogle Scholar
  • 14 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: 688-697
    CrossrefPubMedGoogle Scholar
  • 15 Eder M, Wangler B, Knackmuss S et al. Tetrafluorophenolate of HBED-CC: a versatile conjugation agent for 68Ga-labeled small recombinant antibodies. Eur J Nucl Med Mol Imaging 2008; 35: 1878-1886
    CrossrefPubMedGoogle Scholar
  • 16 Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem 2004; 91: 528-539
    CrossrefPubMedGoogle Scholar
  • 17 Graham K, Kettschau G, Gromov A et al. [18F]-labeled PET tracer BAY1075553, small molecule inhibitor of PSMA for molecular Imaging of prostate cancer. World. Molecular. Imaging. Conference 2011; 235
    PubMedGoogle Scholar
  • 18 Haffner MC, Kronberger IE, Ross JS et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Human Pathology 2009; 40: 1754-1761
    CrossrefPubMedGoogle Scholar
  • 19 Hillier SM, Kern AM, Maresca KP 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: 1082-1093
    PubMedGoogle Scholar
  • 20 Hillier SM, Maresca KP, Femia FJ et al. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Research 2009; 69: 6932-6940
    CrossrefPubMedGoogle Scholar
  • 21 Hofer C, Laubenbacher C, Block T et al. Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. European Urology 1999; 36: 31-35
    PubMedGoogle Scholar
  • 22 Jadvar H. Prostate cancer: PET with 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline. J Nucl Med 2011; 52: 81-89
    CrossrefPubMedGoogle Scholar
  • 23 Kozikowski AP, Nan F, Conti P et al. Design of remarkably simple, yet potent urea-based inhibitors of glutamate carboxypeptidase II (NAALADase) [1]. Journal of Medicinal Chemistry 2001; 44: 298-301
    CrossrefPubMedGoogle Scholar
  • 24 Li Y, Cozzi PJ, Russell PJ. Promising tumor-associated antigens for future prostate cancer therapy. Med Res Rev 2010; 30: 67-101
    PubMedGoogle Scholar
  • 25 Liu H, Moy P, Kim S et al. Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res 1997; 57: 3629-3634
    PubMedGoogle Scholar
  • 26 Maresca KP, Hillier SM, Femia FJ et al. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. Journal of Medicinal Chemistry 2009; 52: 347-357
    CrossrefPubMedGoogle Scholar
  • 27 Mease RC, Dusich CL, Foss CA et al. N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-L-cysteine, [18F]DCFBC: a new imaging probe for prostate cancer. Clin Cancer Res 2008; 14: 3036-3043
    CrossrefPubMedGoogle Scholar
  • 28 Mease RC, Foss CA, Pomper MG. PET imaging in prostate cancer: focus on prostate-specific membrane antigen. Curr Top Med Chem 2013; 13: 951-962
    CrossrefPubMedGoogle Scholar
  • 29 Osborne JR, Akhtar NH, Vallabhajosula S et al. Prostate-specific membrane antigen-based imaging. Urol Oncol 2013; 31: 144-154
    CrossrefPubMedGoogle Scholar
  • 30 Parker C. Active surveillance: towards a new paradigm in the management of early prostate cancer. Lancet Oncol 2004; 5: 101-106
    CrossrefPubMedGoogle Scholar
  • 31 Perner S, Hofer MD, Kim R et al. Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol 2007; 38: 696-701
    CrossrefPubMedGoogle Scholar
  • 32 Picchio M, Briganti A, Fanti S et al. The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol 2011; 59: 51-60
    CrossrefPubMedGoogle Scholar
  • 33 Rajasekaran SA, Anilkumar G, Oshima E et al. A Novel Cytoplasmic Tail MXXXL Motif Mediates the Internalization of Prostate-specific Membrane Antigen. Molecular Biology of the Cell 2003; 14: 4835-4845
    CrossrefPubMedGoogle Scholar
  • 34 Reske SN, Winter G, Baur B et al. Comment on Afshar-Oromieh et al.: PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 2013; 40: 969-970
    CrossrefPubMedGoogle Scholar
  • 35 Robert Koch-Institut (Hrsg.) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg.). 2013 Krebs in Deutschland 2009/2010. Berlin
    PubMed
  • 36 Ross AE, Loeb S, Landis P et al. Prostate-specific antigen kinetics during follow-up are an unreliable trigger for intervention in a prostate cancer surveillance program. J Clin Oncol 2010; 28: 2810-2816
    CrossrefPubMedGoogle Scholar
  • 37 Ross JS, Sheehan CE, Fisher HA et al. Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res 2003; 9: 6357-6362
    PubMedGoogle Scholar
  • 38 Silver DA, Pellicer I, Fair WR et al. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clinical Cancer Research 1997; 3: 81-85
    PubMedGoogle Scholar
  • 39 Smith-Jones PM, Vallabhajosula S, Navarro V et al. Radiolabeled monoclonal antibodies specific to the extracellular domain of prostate-specific membrane antigen: Preclinical studies in nude mice bearing LNCaP human prostate tumor. Journal of Nuclear Medicine 2003; 44: 610-617
    PubMedGoogle Scholar
  • 40 Stephenson AJ, Scardino PT, Kattan MW et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 2007; 25: 2035-2041
    CrossrefPubMedGoogle Scholar
  • 41 Tagawa ST, Milowsky MI, Morris M et al. Phase II study of lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clinical Cancer Research 2013; 19: 5182-5191
    CrossrefPubMedGoogle Scholar
  • 42 Trock BJ, Han M, Freedland SJ et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA 2008; 299: 2760-2769
    CrossrefPubMedGoogle Scholar
  • 43 Troyer JK, Beckett ML, Wright Jr GL. Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. International Journal of Cancer 1995; 62: 552-558
    CrossrefPubMedGoogle Scholar
  • 44 Wang W, Tavora F, Sharma R et al. PSMA expression in Schwannoma: a potential clinical mimicker of metastatic prostate carcinoma. Urol Oncol 2009; 27: 525-528
    CrossrefPubMedGoogle Scholar
  • 45 Wirth M, Weißbach L, Ackermann R et al. Interdisziplinäre Leitlinie der Qualität S3 Zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms. Aktualisierung 2011. Deutsche Gesellschaft für Urologie e. V. 2011
    PubMedGoogle Scholar
  • 46 Wright Jr GL, Grob BM, Haley C et al. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology 1996; 48: 326-334
    CrossrefPubMedGoogle Scholar