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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.[1] It has the potential to provide highly targeted treatment, especially to microscopic tumour cells. Targets include leukemias, lymphomas, gliomas, melanoma, and peritoneal carcinomatosis.[2] 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.[3]
It has been said that "α-emitters are indispensable with regard to optimisation of strategies for tumour therapy".[4]
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).[5] 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.[6]
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.[7][8]
Some α emitting isotopes such as 225Ac and 213Bi are only available in limited quantities from 229Th decay, although cyclotron production is feasible.[9][10][11] Among alpha-emitting radiometals according to availability, chelation chemistry, and half-life, 212Pb is also a promising candidate for targeted alpha-therapy.[12][13]
The ARRONAX cyclotron can produce 211At by irradiation of 209Bi.[14][9]
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.[9]
Treatment of peritoneal carcinomas has promising early results limited by availability of α-emitters compared to β-emitters.[4]
223Ra was the first α-emitter approved by the FDA in the United States for treatment of bone metastases from prostate cancer, and is a recommended treatment in the UK by NICE.[3][15] In a phase III trial comparing 223Ra to a placebo, survival was significantly improved.[16]
Early trials of 225Ac and 213Bi have shown evidence of anti-tumour activity in Leukaemia patients.[17]
Phase I trials on melanomas have shown 213Bi is effective in causing tumour regression.[18][19]
The short path length of alpha particles in tissue, which makes them well suited to treatment of the above types of disease, is a negative when it comes to treatment of larger bodies of solid tumour by intravenous injection.[20][21] Potential methods to solve this problem of delivery exist, such as direct intratumoral injection[22] and anti-angiogenic drugs.[23][3] Limited treatment experience of low grade malignant gliomas has shown possible efficacy.[24]
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