Radioimmunotherapy with a- particle- emitting radionuclides

-particle-emitting radionuclides are highly cytotoxic and are thus promising candidates for use in targeted radioimmunotherapy of cancer. Due to their high linear energy transfer (LET) combined with a short path length in tissue, -particles cause severe DNA double-strand breaks that are repaired inaccurately and finally trigger cell death. For radioimmunotherapy, -emitters such as Ac-225, At-211, Bi-212/Pb-212, Bi-213 and Th-227 are coupled to antibodies via appropriate chelating agents. The -emitter immunoconjugates preferably target proteins that are overexpressed or exclusively expressed on cancer cells. Application of -emitter immunoconjugates seems particularly promising in treatment of disseminated cancer cells and small tumor cell clusters that are released during the resection of a primary tumor. -emitter immunoconjugates have been successfully administered in numerous experimental studies for therapy of ovarian, colon, gastric, blood, breast and bladder cancer. Initial clinical trials evaluating -emitter immunoconjugates in terms of toxicity and therapeutic efficacy have also shown positive results in patients with melanoma, ovarian cancer, acute myeloid lymphoma and glioma. The present problems in terms of availability of therapeutically effiective -emitters will presumably be solved by use of alternative production routes and installation of additional production facilities in the near future. Therefore, clinical establishment of targeted -emitter radioimmunotherapy as one part of a multimodal concept for therapy of cancer is a promising, middle-term concept.