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

radionuclide A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess numbers of either neutrons or protons, giving it excess nuclear energy, and making it unstable. This excess energy can be used in one of three ...

therapy of various

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s. It employs

radioactive Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is conside ...

substances which undergo

alpha decay Alpha decay or α-decay is a type of radioactive decay in which an atomic nucleus emits an alpha particle (helium nucleus). The parent nucleus transforms or "decays" into a daughter product, with a mass number that is reduced by four and an a ...

to treat diseased tissue at close proximity. It has the potential to provide highly targeted treatment, especially to

microscopic The microscopic scale () is the scale of objects and events smaller than those that can easily be seen by the naked eye, requiring a lens or microscope to see them clearly. In physics, the microscopic scale is sometimes regarded as the scale betwe ...

tumour A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...

cells. Targets include

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

glioma A glioma is a type of primary tumor that starts in the glial cells of the brain or spinal cord. They are malignant but some are extremely slow to develop. Gliomas comprise about 30% of all brain and central nervous system tumors and 80% of ...

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

, and peritoneal carcinomatosis. As in diagnostic

nuclear medicine Nuclear medicine (nuclear radiology, nucleology), is a medical specialty involving the application of radioactivity, radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, ''radiology done inside out'', ...

, appropriate radionuclides can be chemically bound to a targeting

biomolecule A biomolecule or biological molecule is loosely defined as a molecule produced by a living organism and essential to one or more typically biological processes. Biomolecules include large macromolecules such as proteins, carbohydrates, lipids ...

which carries the combined

radiopharmaceutical Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...

to a specific treatment point. It has been said that "α-emitters are indispensable with regard to optimisation of strategies for tumour therapy".

Advantages of alpha emitters

The primary advantage of

alpha particle Alpha particles, also called alpha rays or alpha radiation, consist of two protons and two neutrons bound together into a particle identical to a helium-4 nucleus. They are generally produced in the process of alpha decay but may also be produce ...

(α) emitters over other types of radioactive sources is their very high

linear energy transfer In dosimetry, linear energy transfer (LET) is the amount of energy that an ionizing particle transfers to the material traversed per unit distance. It describes the action of radiation into matter. It is identical to the retarding force acting o ...

(LET) and

relative biological effectiveness In radiobiology, the relative biological effectiveness (often abbreviated as RBE) is the ratio of biological effectiveness of one type of ionizing radiation relative to another, given the same amount of absorbed energy. The RBE is an empirical ...

(RBE).

Beta particle A beta particle, also called beta ray or beta radiation (symbol β), is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus, known as beta decay. There are two forms of beta decay, β− decay and � ...

(β) emitters such as

yttrium-90 Yttrium-90 () is a radioactive isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the ...

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 DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...

to DNA molecules, which is one of several effective causes of

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as di ...

Production

Some α emitting isotopes such as ²²⁵Ac and ²¹³Bi are only available in limited quantities from ²²⁹Th decay, although

cyclotron A cyclotron is a type of particle accelerator invented by Ernest Lawrence in 1929–1930 at the University of California, Berkeley, and patented in 1932. Lawrence, Ernest O. ''Method and apparatus for the acceleration of ions'', filed: Januar ...

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.

Applications

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

half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...

that is long enough to provide a therapeutic dose without remaining long enough to damage healthy tissue.

Immunotherapy

Several radionuclides have been studied for use in

immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

. Though β-emitters are more popular, in part due to their availability, trials have taken place involving ²²⁵Ac, ²¹¹At, ²¹²Pb and ²¹³Bi.

Peritoneal carcinomas

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

Bone metastases

²²³Ra was the first α-emitter approved by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

in the United States for treatment of bone metastases from

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

, and is a recommended treatment in the UK by

NICE Nice ( ; ) is a city in and the prefecture of the Alpes-Maritimes department in France. The Nice agglomeration extends far beyond the administrative city limits, with a population of nearly one million In a phase III trial comparing ²²³Ra to a

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

, survival was significantly improved.

Leukaemia

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

Leukaemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

patients.

Melanomas

Phase I trials on

s have shown ²¹³Bi is effective in causing tumour regression.

Solid tumours

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 A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

by intravenous injection. Potential methods to solve this problem of delivery exist, such as direct intratumoral injection and anti-angiogenic drugs. Limited treatment experience of low grade malignant

s has shown possible efficacy.

References

{{Nuclear technology Nuclear technology Nuclear medicine Medical physics Cancer treatments