Targeted alpha-particle therapy

Targeted alpha-particle therapy (or TAT) is an in-development method of targeted radionuclide therapy of various cancers. It employs radioactive substances which undergo alpha decay to treat diseased tissue at close proximity. It has the potential to provide highly targeted treatment, especially to microscopic tumour cells. Targets include leukemias, lymphomas, gliomas, melanoma, and peritoneal carcinomatosis. As in diagnostic nuclear medicine, appropriate radionuclides can be chemically bound to a targeting biomolecule which carries the combined radiopharmaceutical to a specific treatment point. It has been said that "α-emitters are indispensable with regard to optimisation of strategies for tumour therapy". The primary advantage of alpha particle (α) emitters over other types of radioactive sources is their very high linear energy transfer (LET) and relative biological effectiveness (RBE). Beta particle (β) emitters such as yttrium-90 can travel considerable distances beyond the immediate tissue before depositing their energy, while alpha particles deposit their energy in 70–100 μm long tracks. Alpha particles are more likely than other types of radiation to cause double-strand breaks to DNA molecules, which is one of several effective causes of cell death. Some α emitting isotopes such as 225Ac and 213Bi are only available in limited quantities from 229Th decay, although cyclotron production is feasible. Among alpha-emitting radiometals according to availability, chelation chemistry, and half-life, 212Pb is also a promising candidate for targeted alpha-therapy. The ARRONAX cyclotron can produce 211At by irradiation of 209Bi. Though many α-emitters exist, useful isotopes would have a sufficient energy to cause damage to cancer cells, and a half-life that is long enough to provide a therapeutic dose without remaining long enough to damage healthy tissue. Several radionuclides have been studied for use in immunotherapy. Though β-emitters are more popular, in part due to their availability, trials have taken place involving 225Ac, 211At, 212Pb and 213Bi.