Neue und bewährte Radiopharmaka für die Diagnostik und Therapie des Prostatakarzinoms

Zusammenfassung

Ziel: In diesem Beitrag wird ein Überblick über den aktuellen Stand der radiopharmazeutischen Forschung in Bezug auf die Entwicklung von Radiopharmaka für die Diagnostik und Therapie des Prostatakarzinoms (PCa) gegeben.

Material und Methode: Hierzu wurden die jüngsten Entwicklungen zusammengestellt und mit besonderem Augenmerk auf die klinische Anwendung am Patienten bewertet und kommentiert.

Ergebnisse: Zahlreiche Radiopharmaka, die seit einiger Zeit für die klinische Positronenemissionstomografie (PET) und Single-Photonen-Emissionstomografie (SPECT) Diagnostik des PCa eingesetzt werden, adressieren PCa-assoziierte metabolische Prozesse mit einer mehr oder minder ausgeprägten Spezifität. Beispiele für diese Gruppe von Radiopharmaka sind [¹⁸F]Fluorid, [¹¹C]Acetat, [¹⁸F]Fluoroethylcholin ([¹⁸F]FEC), [¹⁸F]Fluoromethylcholin ([¹⁸F]FMC) und [¹¹C]Cholin. Einen neuen Tracer dieses Typs stellt die künstliche Aminosäure anti-1-amino-3-[¹⁸F]fluorocyclobutan-1-carbonsäure ([¹⁸F]FACBC) dar. Hierneben werden vornehmlich spezifische Rezeptorliganden, wie 16β-[¹⁸F]fluoro-5α-dihydrotestosteron ([¹⁸F]FDHT), radiomarkierte GRPR-Liganden (Gastrin Releasing Peptide Rezeptor, BB2) und radiomarkierte Antikörper gegen das Prostata-spezifische Membranantigen (PSMA, NAALADase I oder Glutamat-Carboxypeptidase II) sowie PSMA-spezifische Inhibitoren untersucht. Für die Therapie des PCa kommen in jüngster Zeit PSMA-gerichtete Antikörper und Inhibitoren zum Einsatz, während für die Radionuklidtherapie ossärer Metastasen in 2014 [²²³Ra]RaCl₂ (Xofigo) die FDA- und EMA-Zulassung erhielt.

Schlussfolgerungen: Während einige ‚metabolische’ Radiopharmaka nur mäßigen Erfolg in klinischen Studien zeigten, stehen mit den jüngst entwickelten PSMA-Inhibitoren, PSMA-bindenden höhermolekularen Radiopharmaka (Antikörper und deren Fragmente) und GRPR-Liganden besonders aussichtsreiche neue Tracer-Klassen für die Diagnostik und Radionuklidtherapie des PCa zur Verfügung. Trotz der bisher herausragenden Ergebnisse mit PSMA-Inhibitoren werden groß angelegte Vergleichsstudien eine vergleichende Bewertung mit GRPR-Liganden erlauben.

Abstract

Goal: This paper gives an overview of the radiopharmaceutical research in the development of radiopharmaceuticals in diagnosis and therapy of prostate cancer (PCa).

Materials and methods: Recent developments were summarized, evaluated and annotated with respect to clinical application in patients.

Results: In clinical positron-emission tomography (PET) and single-photon-emission computed tomography (SPECT) diagnostics of PCa, a variety of radiopharmaceuticals are addressing metabolic processes with higher or lower specificity. Examples of metabolic radiopharmaceuticals are [¹⁸F]fluoride, [¹¹C]acetate, [¹⁸F]fluoroethylcholine ([¹⁸F]FEC), [¹⁸F]fluoromethylcholine ([¹⁸F]FMC) und [¹¹C]choline. A new metabolic tracer is the artificial amino acid anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid ([¹⁸F]FACBC). Additionally, receptor-specific ligands, such as 16β-[¹⁸F]fluoro-5α-dihydrotestosterone ([¹⁸F]FDHT), radiolabeled GRPR ligands (Gastrin Releasing Peptide, BB2) and radiolabeled antibodies against prostate-specific membrane antigen (PSMA, NAALADase I or glutamate carboxypeptidase II), as well as PSMA-specific inhibitors are under evaluation. Recently, PSMA-directed antibodies and inhibitors were introduced for therapy of PCa, and in 2014 [²²³Ra]RaCl₂ (Xofigo) was approved for radionuclide therapy of bone metastases by the FDA and the EMA.

Conclusion: Whereas some ‚metabolic‘ radiopharmaceuticals revealed moderate success in clinical studies, recently developed PSMA inhibitors, PSMA-directed high molecular weight radiopharmaceuticals (antibodies and antibody fragments) and GRPR ligands represent very promising tracer classes for diagnosis and radionuclide therapy of PCa. The outstanding results with PSMA inhibitors need to be elaborated in a large-scale comparative study to show their clinical potential in comparison to GRPR ligands.

Schlüsselwörter

Prostatakarzinom - Endoradiotherapie - Bildgebung - Patient

Key words

prostate cancer - endoradiotherapy - imaging - patient

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