Diffusing alpha emitters radiation therapy

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Diffusing Alpha-emitters Radiation Therapy or DaRT is an alpha-particle-based radiation therapy for the treatment of solid tumors. [1] [2]

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This therapy was developed at Tel Aviv University in Israel, by Professors Itzhak Kelson and Yona Keisari. The treatment is delivered by the intratumoral insertion of metal tubes called “seeds”, which have Radium-224 atoms fixed to their surface. When the radium decays, its short-lived daughter Radon-220 is released from the seed through recoil energy. [3] The daughters of Radon-220, in particular Pb-212, disperse in the tumor, and emit high-energy alpha particles, which destroy the tumor. Because the alpha-emitting atoms diffuse only a few millimeters in tissue, the DaRT eradicates the tumor cells and spares the surrounding healthy tissue. [3]

Alpha radiation

Alpha radiation is a nuclear phenomenon in which a heavy radionuclide emits an energetic alpha particle (consisting of two protons and two neutrons) and transmutes to a different radionuclide. The emitted alpha particle has a range in tissue of only 40-90 microns, which minimizes collateral damage when used for treatment purposes. However, this also limits its ability to destroy tumors that are many millimeters in diameter. Alpha radiation possesses a potent cell-killing capability because it has a high linear energy transfer (LET) which translates into a high Relative Biological Effectiveness (RBE). [4]

Treatment of cancer

The invention of DaRT makes possible the use of alpha radiation for treating solid tumors, because it overcomes the range limitation of alpha particles in tissue. The daughter atoms of Radium-224 can each diffuse several millimeters in tumor tissue, while emitting alpha particles. The tumor-killing capability of DaRT comes mainly from the ability of alpha radiation to irreparably break the double stranded DNA in tumor cells. [5] This capability does not seem to be dependent on the stage of the cell cycle or the level of oxygenation of the cancer cell.[ citation needed ]

Preclinical studies in multiple tumor types

Preclinical studies have demonstrated that DaRT can effectively damage all solid tumor types. Studies of 10 different tumor types in mice demonstrated that all responded to DaRT. [6] [7] [8] [9] [10] [11] [12] [ excessive citations ]

Combination therapy of DaRT with either chemotherapy or immunotherapy

In preclinical studies, DaRT effectiveness was enhanced when combined with standard chemotherapies such as 5-FU. In addition, DaRT was able to turn the tumor into its own vaccine and stimulate a systemic anti-tumor immune response. [13] This immune response was effectively augmented by addition of immunostimulants and/or inhibitors of immunosuppressive cells. This immune effect was observed not only as enhanced local tumor destruction at the primary tumor site, but also by elimination of tumor metastases in the lungs. [12] [14] These results suggest that DaRT combined with immunotherapy induces a tumor-specific systemic immune response.[ citation needed ]

Treatment of solid tumors in human patients with DaRT

The first results of the DaRT in human patients, from a pilot study of 28 patients by Prof. Popovtzer (Israel) and Dr. Bellia (Italy), were published in 2020. [15] From among this cohort of elderly patients (median age, 80.5 years), 61% had recurrent and previously treated tumors, including 42% who were radioresistant from prior therapy. Patients were diagnosed with histopathologically confirmed squamous cell carcinoma of the skin or head and neck. One-hundred percent of tumors responded to DaRT, with complete responses occurring in greater than 78% of cases, and no major toxicity was noted. Thirty days after treatment, there was no measurable radioactivity in the blood or urine of patients. Additional studies in larger populations are now ongoing to strengthen support regarding the safety and effectiveness of this technique of intratumoral alpha radiation-based tumor ablation.[ citation needed ]

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Actinium is a chemical element with the symbol Ac and atomic number 89. It was first isolated by Friedrich Oskar Giesel in 1902, who gave it the name emanium; the element got its name by being wrongly identified with a substance André-Louis Debierne found in 1899 and called actinium. Actinium gave the name to the actinide series, a set of 15 elements between actinium and lawrencium in the periodic table. Together with polonium, radium, and radon, actinium was one of the first non-primordial radioactive elements to be isolated.

<span class="mw-page-title-main">Alpha decay</span> Type of radioactive decay

Alpha decay or α-decay is a type of radioactive decay in which an atomic nucleus emits an alpha particle and thereby transforms or 'decays' into a different atomic nucleus, with a mass number that is reduced by four and an atomic number that is reduced by two. An alpha particle is identical to the nucleus of a helium-4 atom, which consists of two protons and two neutrons. It has a charge of +2 e and a mass of 4 Da. For example, uranium-238 decays to form thorium-234.

<span class="mw-page-title-main">Polonium</span> Chemical element, symbol Po and atomic number 84

Polonium is a chemical element with the symbol Po and atomic number 84. A rare and highly radioactive metal with no stable isotopes, polonium is a chalcogen and chemically similar to selenium and tellurium, though its metallic character resembles that of its horizontal neighbors in the periodic table: thallium, lead, and bismuth. Due to the short half-life of all its isotopes, its natural occurrence is limited to tiny traces of the fleeting polonium-210 in uranium ores, as it is the penultimate daughter of natural uranium-238. Though longer-lived isotopes exist, such as the 125.2 years half-life of polonium 209, they are much more difficult to produce. Today, polonium is usually produced in milligram quantities by the neutron irradiation of bismuth. Due to its intense radioactivity, which results in the radiolysis of chemical bonds and radioactive self-heating, its chemistry has mostly been investigated on the trace scale only.

<span class="mw-page-title-main">Radium</span> Chemical element, symbol Ra and atomic number 88

Radium is a chemical element with the symbol Ra and atomic number 88. It is the sixth element in group 2 of the periodic table, also known as the alkaline earth metals. Pure radium is silvery-white, but it readily reacts with nitrogen (rather than oxygen) upon exposure to air, forming a black surface layer of radium nitride (Ra3N2). All isotopes of radium are radioactive, the most stable isotope being radium-226 with a half-life of 1,600 years. When radium decays, it emits ionizing radiation as a by-product, which can excite fluorescent chemicals and cause radioluminescence.

<span class="mw-page-title-main">Radiation therapy</span> Therapy using ionizing radiation, usually to treat cancer

Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body, and have not spread to other parts. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor. Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. A physician who practices in this subspecialty is a radiation oncologist.

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Radioactive decay is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is considered radioactive. Three of the most common types of decay are alpha, beta, and gamma decay, all of which involve emitting particles. The weak force is the mechanism that is responsible for beta decay, while the other two are governed by the electromagnetism and nuclear force.

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<span class="mw-page-title-main">Geiger–Marsden experiments</span> Experiments proving existence of atomic nuclei

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Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell. It is a form of unsealed source radiotherapy. In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells. The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues. By its nature, RIT requires a tumor cell to express an antigen that is unique to the neoplasm or is not accessible in normal cells.

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<span class="mw-page-title-main">Gamma ray</span> Energetic electromagnetic radiation arising from radioactive decay of atomic nuclei

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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 produced in other ways. Alpha particles are named after the first letter in the Greek alphabet, α. The symbol for the alpha particle is α or α2+. Because they are identical to helium nuclei, they are also sometimes written as He2+
or 4
2
He2+
indicating a helium ion with a +2 charge. Once the ion gains electrons from its environment, the alpha particle becomes a normal helium atom 4
2
He
.

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<span class="mw-page-title-main">Peptide receptor radionuclide therapy</span> Type of radiotherapy

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