Systemic targeted alpha radiotherapy for cancer

The fundamental principles of internal targeted alpha-therapy for cancer were established many decades ago. The high linear energy transfer (LET) of alpha radiation to the targeted cancer cells causes double strand breaks in DNA. At the same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and chemotherapy. Such therapies fail on several fronts, such as lack of control of some primary cancers (e.g., glioblastoma multiforme) and inhibition of the development of lethal metastatic cancer after successful treatment of the primary cancer. This review describes the developing role of systemic high LET, internal radiation therapy. Targeted alpha-therapy (TAT) is a rapidly advancing experimental therapy that holds promise to deliver high cytotoxicity to targeted cancer cells. Initially thought to be indicated for leukaemia and micrometastases, there is now evidence that solid tumours can also be regressed. Alpha therapy may be molecular or physiological in its targeting. Alpha emitting radioisotopes such as 212Bi, 213Bi, 211At and 225Ac are used to label monoclonal antibodies or proteins that target specific cancer cells. Alternatively, 233Ra is used for palliative therapy of breast and prostate cancers because of its bone-seeking properties. Preclinical studies and clinical trials of alpha-therapy are discussed for leukaemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer and pancreatic cancers.