Radiomarkierte Peptide zur bildgebenden Diagnostik und Radiotherapie von Tumoren

Zusammenfassung

Radioaktiv markierte Peptide leisten einen wertvollen Beitrag auf dem Weg zur individualisierten, auf den Patienten zugeschnittenen Behandlung maligner Erkrankungen. Wegen ihrer exzellenten Zielerkennung sowie der einfach durchzuführenden Radiomarkierung dieser synthetischen Moleküle sind Radiopeptide für die Patientenselektion (Diagnose) und die interne Bestrahlung (Therapie) besonders geeignet. Sowohl radiohalogen- als auch radiometallmarkierte Peptide wurden erfolgreich zur Diagnose und Therapie einer Vielzahl von Tumoren eingesetzt. Das Potenzial von Radiopeptiden konnte besonders mit ⁹⁰Y-DOTATOC und ¹⁷⁷Lu-DOTATATE bei der Behandlung von konventionell austherapierten Patienten mit somatostatinrezeptorpositiven, neuroendokrinen Tumoren gezeigt werden. ^99mTc-NeoTect®, ein weiteres SSTR-bindendes Peptid-Radiometall-Konjugat, ist in der Lage, Lungenläsionen mittels SPECT mit 97 % Sensitivität und > 70 % Spezifität zu detektieren. In verschiedenen präklinischen Lungentumormodellen konnte auch mit ¹⁸⁸Re-NeoTide®, dem therapeutischen Pendant zu ^99mTc NeoTect®, eine signifikante Tumorregression in Lungentumormodellen erreicht werden. Die zielgerichtete Detektion der Neoangiogenese mittels α_vβ₃-Rezeptorbindung macht Radiopeptide zu wirkungsvollen Werkzeugen für die diagnostische Bildgebung, da dieser Rezeptor bei der Blutgefäßneubildung vielfältiger Tumorentitäten verstärkt gefunden wird. Die Verwendung von (¹⁸F)-Galakto-RGD, einem hochaffinen Binder für α_vβ₃-Rezeptoren, unterstreicht das Potenzial von Radiopeptiden zur Tumordetektion und zum Staging. Der erfolgreiche Einsatz von ^99mTc-Demogastrin® bei der Detektion des medullären Schilddrüsenkarzinoms und multipler Metastasen öffnet ein weiteres Feld zur Diagnose und Therapie von soliden Tumoren.

Abstract

Radioactively labeled peptides are powerful tools for an individualized, patient based treatment of oncological diseases. The excellent targeting concomittant with the easy radiolabeling enable such fully synthetic molecules for patient selection (diagnosis) and internal irradiation (therapy). Peptides labeled with radiohalogenes as well as radiometals were used successfully for the diagnosis and therapy of numerous malignancies. The use of ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE for the treatment of patients with neuroendocrine tumors, refrectory to chemotherapy, underline the potential of radiopeptides. ^99mTc-NeoTect®, another somatostatin targeting peptide-radiometal conjugate, detects lung lesions with 97 % sensitivity and > 70 % specificity employing SPECT. Pre-clinical results of ¹⁸⁸Re-NeoTide®, the radiotherapeutic counterpart of ^99mTc-NeoTect®, indicate significant tumor regression in lung tumor models. The α_vβ₃-targeted detection of neoangiogenesis proves radiopeptides to be valuable tools for the diagnostic imaging of multiple tumor entities, since α_vβ₃-receptors are overexpressed in a variety of tumors undergoing new blood-vessel formation. The application of (¹⁸F)-Galacto-RGD, a high-affinity binder for α_vβ₃-receptors, pinpoints the potential of peptides for tumor detection (Fig. [5]) and staging. The successful use of ^99mTc-Demogastrin® for detection of medullary thyroid carcinoma and its multiple metastases opens a new field in diagnosis and therapy of solid tumors.

Tumordiagnostik - SPECT - PET - Radiotherapie - Radiopeptide

tumor diagnosis - SPECT - PET - radiotherapy - radiopeptides

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