Targeted alpha-particle therapy

Source: Wikipedia, the free encyclopedia.

Targeted alpha-particle therapy (or TAT) is an in-development method of targeted

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]

Advantages of alpha emitters

Comparison of range of α (red) and β− (white) particles

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]

Production

Some α emitting isotopes such as

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]

Applications

Though many α-emitters exist, useful isotopes would have a sufficient energy to cause damage to cancer cells, and a

dose
without remaining long enough to damage healthy tissue.

Immunotherapy

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]

Peritoneal carcinomas

Treatment of peritoneal carcinomas has promising early results limited by availability of α-emitters compared to β-emitters.[4]

Bone metastases

phase III trial comparing 223Ra to a placebo, survival was significantly improved.[16]

Leukaemia

Early trials of 225Ac and 213Bi have shown evidence of anti-tumour activity in

Leukaemia patients.[17]

Melanomas

Phase I trials on melanomas have shown 213Bi is effective in causing tumour regression.[18][19]

Solid tumours

The short

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]

See also

References

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  15. ^ "Radium-223 dichloride for treating hormone-relapsed prostate cancer with bone metastases". National Institute for Health and Care Excellence. 28 September 2016. Retrieved 19 December 2016.
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