Molekulare Radiotherapie mit neuen Radiopharmaka: Präzisionsonkologie zur personalisierten Patientenbehandlung

Zusammenfassung

Maligne Erkrankungen sind mit Veränderungen auf der molekularen Ebene assoziiert. Präzisionsonkologie meint einen personalisierten Therapieansatz, der auf spezifische molekulare Signale in Tumorzellen abzielt und mit optimaler Wirksamkeit bei minimalen Nebenwirkungen verbunden ist. Tumore können hochwirksam mit Radiopharmaka behandelt werden, die auf spezifische, zelluläre Mechanismen abzielen (z. B. Metastasen von gut differenzierten neuroendokrinen Neoplasmen mittels ¹⁷⁷Lu markierten Somatostatinanaloga). Die molekulare Bildgebung mit PET/CT oder PET/MRT spielt eine entscheidende Rolle bei der Patientenauswahl sowie bei der Überwachung des Therapieansprechens und ist daher in der Lage, die molekulare Radiotherapie zu steuern („wir sehen, was wir behandeln“ und umgekehrt). Theranostik in der Nuklearmedizin fügt sich daher in die Definition der Präzisionsonkologie ein, da sie beispielhaft die Kombination von molekularer Bildgebung und molekularer Radiotherapie beinhaltet, wobei derselbe Vektor, markiert mit unterschiedlichen Radionukliden, zum einen für die Diagnose und zum anderen für die Behandlung verwendet wird. Während die Anwendung von ¹³¹I durch Saul Hertz Mitte des letzten Jahrhunderts erstmals den Weg für eine gezielte molekulare Radiotherapie eröffnete, fasst dieser Übersichtsartikel die Therapie mit in den letzten Jahren neuentwickelten Radiopharmaka zusammen.

Abstract

Cancer is associated with alterations at the molecular level. Precision oncology refers to a personalized therapy approach, which targets specific molecular signals in tumor cells, and is associated with maximal efficacy and minimal side effects. Tumors can be effectively treated using radiopharmaceuticals, which specifically target cellular mechanisms, for e. g., treatment of metastases of well-differentiated neuroendocrine neoplasms using ¹⁷⁷Lu labelled somatostatin analogs. Molecular imaging with PET/CT or PET/MRI plays a vital role in patient selection as well as monitoring of therapy response and therefore is able to guide molecular radiotherapy (“we see what we treat” and vice versa). Theranostics in nuclear medicine therefore is part of precision oncology, because it exemplifies the combination of molecular imaging and molecular radiotherapy, utilizing the same vector with distinct radionuclides for diagnosis and treatment, respectively. Whereas ¹³¹I (conceived for medical use by Saul Hertz in 1936) paved the way to targeted molecular radiotherapy around the middle of the previous century, this review summarizes the clinical use of novel radiopharmaceuticals developed over the last two decades.

Schlüsselwörter

Theranostik - peptidvermittelte Radiorezeptortherapie (PRRT) - Präzisionsonkologie - PSMA-Radioligandentherapie (PRLT) - personalisierte Therapie - therapeutische Radioisotope - PSMA - DOTATOC - mCRPC - Prostatakarzinom - neuroendokriner Tumor - Dosimetrie - ¹⁷⁷Lu - ⁹⁰Y - ²²⁵Ac - ²¹³Bi

Keywords

theranostics - peptide receptor radionuclide therapy (PRRT) - PSMA radioligand therapy (PRLT) - personalized treatment - therapeutic radioisotopes - PSMA - DOTATOC - mCRPC - prostate cancer - neuroendocrine tumors - dosimetry - ¹⁷⁷Lu - ⁹⁰Y - ²²⁵Ac - ²¹³Bi

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