Zielgerichtete Radionuklidtherapie mit α-Emittern - Grundlagen, experimentelle und erste klinische Studien

Abstract

α-particle emitting nuclides are highly cytotoxic and are thus promising candidates for use in targeted radionuclide therapy of cancer. Due to their high linear energy transfer (LET) combined with a short range in tissue, α-particles cause severe DNA-damages that are repaired inaccurately and finally trigger cell death. For targeted therapy, α-emitters like actinium-225, astatine-211, bismuth-213 and thorium-227 are coupled to antibodies or receptor ligands via appropriate chelators that bind to proteins that are overexpressed or exclusively expressed on tumour cells. Application of α-emitters seems particularly promising for targeted therapy of disseminated tumour cells and small tumour cell clusters that remain in the body following resection of the primary tumour. α-emitter conjugates have been successfully applied in numerous experimental studies for therapy of ovarian, colon, gastric and breast cancer. Initial clinical trials evaluating α-emitter antibody conjugates in terms of tolerance and therapeutic efficacy also have shown positive results in patients with melanoma, ovarian cancer, acute myeloid lymphoma (AML) and glioma. Therefore the aim could be clinical establishment of targeted α-emitter radionuclide therapy as one part of a multimodal concept for therapy of cancer.