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 nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transfer ...

therapy of various

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

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 consi ...

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) and thereby transforms or 'decays' into a different atomic nucleus, with a mass number that is reduced by four and an at ...

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 be ...

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 ...

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

. Targets include

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in 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). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include en ...

glioma A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours. Signs and symptoms ...

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

, and peritoneal carcinomatosis. As in diagnostic

nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is " radiology done inside out" because it records radiation emi ...

, appropriate radionuclides can be chemically bound to a targeting

biomolecule A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or developmental biology, development. Biom ...

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 prod ...

(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 empiric ...

(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 during the process of beta decay. There are two forms of beta decay, � ...

(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.

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 O. 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: Jan ...

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 (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...

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. 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 in the United States for treatment of

bone metastases Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that results from primary tumor invasion to bone. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing's sarcoma are rare; the most co ...

from

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ...

, and is a recommended treatment in the UK by

NICE Nice ( , ; Niçard: , classical norm, or , nonstandard, ; it, Nizza ; lij, Nissa; grc, Νίκαια; la, Nicaea) is the prefecture of the Alpes-Maritimes department in France. The Nice agglomeration extends far beyond the administrative ...

. In a phase III trial comparing ²²³Ra to a

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

, survival was significantly improved.

Leukaemia

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

Leukaemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in 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

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