Thorotrast

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Thorium dioxide Fluorite-unit-cell-3D-ionic.png
Thorium dioxide
Thorotrast bottle Thorotrast.jpg
Thorotrast bottle

Thorotrast is a suspension containing particles of the radioactive compound thorium dioxide, ThO2, that was used as a radiocontrast agent in medical radiography in the 1930s and 1940s. Use in some countries, such as the U.S., continued into the 1950s.

In chemistry, a suspension is a heterogeneous mixture that contains solid particles sufficiently large for sedimentation. The particles may be visible to the naked eye, usually must be larger than one micrometer, and will eventually settle, although the mixture is only classified as a suspension when and while the particles have not settled out. A suspension is a heterogeneous mixture in which the solute particles do not dissolve, but get suspended throughout the bulk of the solvent, left floating around freely in the medium. The internal phase (solid) is dispersed throughout the external phase (fluid) through mechanical agitation, with the use of certain excipients or suspending agents. An example of a suspension would be sand in water. The suspended particles are visible under a microscope and will settle over time if left undisturbed. This distinguishes a suspension from a colloid, in which the suspended particles are smaller and do not settle. Colloids and suspensions are different from solution, in which the dissolved substance (solute) does not exist as a solid, and solvent and solute are homogeneously mixed.

Radioactive decay Process by which an unstable atom emits radiation

Radioactive decay is the process by which an unstable atomic nucleus loses energy by emitting radiation, such as an alpha particle, beta particle with neutrino or only a neutrino in the case of electron capture, or a gamma ray or electron in the case of internal conversion. A material containing unstable nuclei is considered radioactive. Certain highly excited short-lived nuclear states can decay through neutron emission, or more rarely, proton emission.

Thorium dioxide Chemical compound

Thorium dioxide (ThO2), also called thorium(IV) oxide, is a crystalline solid, often white or yellow in color. Also known as thoria, it is produced mainly as a by-product of lanthanide and uranium production. Thorianite is the name of the mineralogical form of thorium dioxide. It is moderately rare and crystallizes in an isometric system. The melting point of thorium oxide is 3300 °C – the highest of all known oxides. Only a few elements (including tungsten and carbon) and a few compounds (including tantalum carbide) have higher melting points. All thorium compounds are radioactive because there are no stable isotopes of thorium.

Contents

Thorium compounds produce excellent images because of thorium's high opacity to X-rays (it has a high cross section for absorption). However, thorium is retained in the body, and it is radioactive, emitting harmful alpha radiation as it decays. Because the suspension offered high image quality and had virtually no immediate side-effects compared to the alternatives available at the time, Thorotrast became widely used after its introduction in 1931. António Egas Moniz contributed to its development. [1] About 2 to 10 million patients worldwide have been treated with Thorotrast. However, today it has shown an increase risk in certain cancers such as cholangiocarcinomas, angiosarcomas, hepatocellular carcinoma and hepatic fibrosis of the liver.

When two particles interact, their mutual cross section is the area transverse to their relative motion within which they must meet in order to scatter from each other. If the particles are hard inelastic spheres that interact only upon contact, their scattering cross section is related to their geometric size. If the particles interact through some action-at-a-distance force, such as electromagnetism or gravity, their scattering cross section is generally larger than their geometric size. When a cross section is specified as a function of some final-state variable, such as particle angle or energy, it is called a differential cross section. When a cross section is integrated over all scattering angles, it is called a total cross section. Cross sections are typically denoted σ (sigma) and measured in units of area.

António Egas Moniz Portuguese neurosurgeon

António Caetano de Abreu Freire Egas Moniz, known as Egas Moniz, was a Portuguese neurologist and the developer of cerebral angiography. He is regarded as one of the founders of modern psychosurgery, having developed the surgical procedure leucotomy—​known better today as lobotomy—​for which he became the first Portuguese national to receive a Nobel Prize in 1949.

Safety

Even at the time of introduction, there was concern about the safety of Thorotrast. Following injection, the drug is distributed to the liver, spleen, lymph nodes, and bone, where it is absorbed. After this initial absorption, redistribution takes place at a very slow pace. Specifically, the biological half-life is estimated to be 22 years. [2] This means that the organs of patients who have been given Thorotrast will be exposed to internal alpha radiation for the rest of their lives. The significance of this long-term exposure was not fully understood at the time of Thorotrast's introduction in 1931.

Liver vital organ in vertebrates and some other animals

The liver is an organ only found in vertebrates which detoxifies various metabolites, synthesizes proteins and produces biochemicals necessary for digestion. In humans, it is located in the right upper quadrant of the abdomen, below the diaphragm. Its other roles in metabolism include the regulation of glycogen storage, decomposition of red blood cells and the production of hormones.

Spleen Internal organ in most vertebrate animals

The spleen is an organ found in virtually all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes from Ancient Greek σπλήν (splḗn).

Lymph node organ of the lymphatic system

A lymph node or lymph gland is an ovoid or kidney-shaped organ of the lymphatic system and the adaptive immune system. Lymph nodes are widely present throughout the body and are linked by the lymphatic vessels as a part of the circulatory system. They are major sites of B and T lymphocytes and other white blood cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles and cancer cells, but they do not have a detoxification function.

Due to the release of alpha particles, Thorotrast was found to be extremely carcinogenic. There is a high over-incidence of various cancers in patients who have been treated with Thorotrast. The cancers occur some years (usually 20–30) after injection of Thorotrast. The risk of developing liver cancer (or bile duct cancer) in former Thorotrast patients has been measured to be well above 100 times the risk of the rest of the population. The risk of leukemia appears to be 20 times higher in Thorotrast patients. [3] Thorotrast exposure has also been associated with the development of angiosarcoma. German patients exposed to Thorotrast had their median life-expectancy shortened by 14 years in comparison to a similar non-exposed control group. [4]

Hepatocellular carcinoma liver carcinoma that has material basis in undifferentiated hepatocytes

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults, and is the most common cause of death in people with cirrhosis.

Cholangiocarcinoma bile duct adenocarcinoma that has material basis in bile duct epithelial cells.

Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stool or dark urine may also occur. Other biliary tract cancers include gallbladder cancer and cancer of the ampulla of Vater.

Leukemia group of cancers that usually begin in the bone marrow

Leukemia, also spelled leukaemia, 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 leukemia cells. Symptoms may include bleeding and bruising, feeling tired, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy.

Thorium is no longer used in X-ray contrast agents. Today, iodinated hydrophilic (water-soluble) molecules are universally used as injected contrast agents in X-ray procedures.

Iodinated contrast

Iodinated contrast is a form of intravenous radiocontrast agent containing iodine, which enhances the visibility of vascular structures and organs during radiographic procedures. Some pathologies, such as cancer, have particularly improved visibility with iodinated contrast.

The Danish director Nils Malmros's movie, Facing the Truth (original Danish title At Kende Sandheden) from 2002, portrays the dilemma that faced Malmros's father, Richard Malmros, when treating his patients in the 1940s. Richard Malmros was deeply concerned about the persistence of Thorotrast in the body but was forced to use Thorotrast, because the only available alternative (per-abrodil) had serious immediate side-effects, suffered from image quality problems and was difficult to obtain during the Second World War. The use of Thorotrast in Denmark ended in 1947 when safer alternatives became available.

Denmark Constitutional monarchy in Europe

Denmark, officially the Kingdom of Denmark, is a Nordic country. Denmark proper, which is the southernmost of the Scandinavian countries, consists of a peninsula, Jutland, and an archipelago of 443 named islands, with the largest being Zealand, Funen and the North Jutlandic Island. The islands are characterised by flat, arable land and sandy coasts, low elevation and a temperate climate. The southernmost of the Scandinavian nations, Denmark lies southwest of Sweden and south of Norway, and is bordered to the south by Germany. The Kingdom of Denmark also includes two autonomous territories in the North Atlantic Ocean: the Faroe Islands and Greenland. Denmark has a total area of 42,924 km2 (16,573 sq mi), land area of 42,394 km2 (16,368 sq mi), and the total area including Greenland and the Faroe Islands is 2,210,579 km2 (853,509 sq mi), and a population of 5.8 million.

Nils Malmros, a Danish film director and screenwriter, is considered a leading auteur of realism in Danish cinema. Malmros is noted for his detailed focus on the common growing pains of adolescence and the loss of innocence, which he draws from his childhood experiences growing up in Århus, Denmark. His most notable films form a trilogy about schoolchildren in 1950s Århus: Lars-Ole 5c, Boys and Tree of Knowledge. The latter film, 1981's Tree of Knowledge, is one of ten films listed in Denmark's cultural canon by the Danish Ministry of Culture.

Danish language North Germanic language spoken in Denmark

Danish is a North Germanic language spoken by around six million people, principally in Denmark and in the region of Southern Schleswig in northern Germany, where it has minority language status. Also, minor Danish-speaking communities are found in Norway, Sweden, Spain, the United States, Canada, Brazil, and Argentina. Due to immigration and language shift in urban areas, around 15–20% of the population of Greenland speak Danish as their first language.

Current use

Thorotrast has also been used in research to stain neural tissue samples for examination by historadiography. [5]

Related Research Articles

Radon Chemical element with atomic number 86

Radon is a chemical element with the symbol Rn and atomic number 86. It is a radioactive, colorless, odorless, tasteless noble gas. It occurs naturally in minute quantities as an intermediate step in the normal radioactive decay chains through which thorium and uranium slowly decay into lead and various other short-lived radioactive elements; radon itself is the immediate decay product of radium. Its most stable isotope, 222Rn, has a half-life of only 3.8 days, making radon one of the rarest elements since it decays away so quickly. However, since thorium and uranium are two of the most common radioactive elements on Earth, and they have three isotopes with very long half-lives, on the order of several billions of years, radon will be present on Earth long into the future in spite of its short half-life as it is continually being generated. The decay of radon produces many other short-lived nuclides known as radon daughters, ending at stable isotopes of lead.

Radiation therapy therapy using ionizing radiation

Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is therapy using ionizing radiation, generally as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. 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.

Brachytherapy Type of radiation therapy

Brachytherapy is a form of radiotherapy where a sealed radiation source is placed inside or next to the area requiring treatment. Brachy is Greek for short distance. Brachytherapy is commonly used as an effective treatment for cervical, prostate, breast, esophageal and skin cancer and can also be used to treat tumours in many other body sites. Treatment results have demonstrated that the cancer-cure rates of brachytherapy are either comparable to surgery and external beam radiotherapy (EBRT) or are improved when used in combination with these techniques. Brachytherapy can be used alone or in combination with other therapies such as surgery, EBRT and chemotherapy.

Soft-tissue sarcoma human disease

A soft-tissue sarcoma(STS), is a form of sarcoma that develops in connective tissue, though the term is sometimes applied to elements of the soft tissue that are not currently considered connective tissue. There are a number of types.

Radiation protection, also known as radiological protection, is defined by the International Atomic Energy Agency (IAEA) as "The protection of people from harmful effects of exposure to ionizing radiation, and the means for achieving this". Exposure can be from a source of radiation external to the human body or due to internal irradiation caused by the ingestion of radioactive contamination.

Radiocontrast agents are substances used to enhance the visibility of internal structures in X-ray-based imaging techniques such as computed tomography, projectional radiography, and fluoroscopy. Radiocontrast agents are typically iodine, or more rarely barium-sulphate. They absorb external X-rays, resulting in decreased exposure on the X-ray detector. This is different from radiopharmaceuticals used in nuclear medicine which emit radiation.

Angiosarcoma malignant Vascular tumor that results in rapidly proliferating, extensively infiltrating anaplastic cells derives from blood vessels and derived from the lining of irregular blood-filled spaces

Angiosarcoma is a cancer of the cells that line the walls of blood vessels or lymphatic vessels. The lining of the vessel walls is called the endothelium. However, they should not be confused with cherry hemangiomas.

Cerebral angiography Angiography that produces images of blood vessels in and around the brain

Cerebral angiography is a form of angiography which provides images of blood vessels in and around the brain, thereby allowing detection of abnormalities such as arteriovenous malformations and aneurysms. It was pioneered in 1927 by the Portuguese neurologist Egas Moniz at the University of Lisbon, who also helped develop thorotrast for use in the procedure.

Iodine-131 (131I) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nuclear energy, medical diagnostic and treatment procedures, and natural gas production. It also plays a major role as a radioactive isotope present in nuclear fission products, and was a significant contributor to the health hazards from open-air atomic bomb testing in the 1950s, and from the Chernobyl disaster, as well as being a large fraction of the contamination hazard in the first weeks in the Fukushima nuclear crisis. This is because I-131 is a major fission product of uranium and plutonium, comprising nearly 3% of the total products of fission. See fission product yield for a comparison with other radioactive fission products. I-131 is also a major fission product of uranium-233, produced from thorium.

Radiophobia obsessive fear of ionizing radiation

Radiophobia is a fear of ionizing radiation. Given that significant doses of radiation are harmful, even deadly, every threat of the radiation exposure may cause significant fear. The term is also used to describe the opposition to the use of nuclear technology arising from concerns disproportionately greater than actual risks would merit.

Actinides in the environment refer to the sources, environmental behaviour and effects of actinides in Earth's environment. Environmental radioactivity is not limited solely to actinides; non-actinides such as radon and radium are of note.

<i>Facing the Truth</i> (film) 2002 film by Nils Malmros

Facing the Truth is a 2002 Danish drama written and directed by Nils Malmros. Shot in black-and-white documentary style, and based on the real life of Malmros' father, the film relates the hardships of a young neurosurgeon struggling through a medical lawsuit. Malmros, whose films are known for their realism, is educated as a surgeon and performed all the film's brain surgery scenes. The film was nominated for the 2003 Bodil Award for Best Danish Film and won the 2003 Danish Film Academy's Robert Award for Film of the Year.

Sirtex company in North Sydney, Australia

Sirtex Medical Limited is an Australian-based medical device company, providing a radioactive treatment for inoperable liver cancer called SIR-Spheres microspheres. The company is currently headed by Andrew McLean, who was appointed as CEO on June 5, 2017. Sirtex was established in 1997.

Liver cancer gastrointestinal system cancer, located in the liver

Liver cancer, also known as hepatic cancer and primary hepatic cancer, is cancer that starts in the liver. Cancer which has spread from elsewhere to the liver, known as liver metastasis, is more common than that which starts in the liver. Symptoms of liver cancer may include a lump or pain in the right side below the rib cage, swelling of the abdomen, yellowish skin, easy bruising, weight loss and weakness.

Radiobiology is a field of clinical and basic medical sciences that involves the study of the action of ionizing radiation on living things, especially health effects of radiation. Ionizing radiation is generally harmful and potentially lethal to living things but can have health benefits in radiation therapy for the treatment of cancer and thyrotoxicosis. Its most common impact is the induction of cancer with a latent period of years or decades after exposure. High doses can cause visually dramatic radiation burns, and/or rapid fatality through acute radiation syndrome. Controlled doses are used for medical imaging and radiotherapy.

Selective internal radiation therapy

Selective internal radiation therapy, also known as transarterial radioembolization (TARE), radioembolization or intra-arterial microbrachytherapy is a form of radiation therapy used in interventional radiology to treat cancer. It is generally for selected patients with surgically unresectable cancers, especially hepatocellular carcinoma or metastasis to the liver. The treatment involves injecting tiny microspheres of radioactive material into the arteries that supply the tumor, where the spheres lodge in the small vessels of the tumor. Because this treatment combines radiotherapy with embolization, it is also called radioembolization. The chemotherapeutic analogue is called chemoembolization, of which transcatheter arterial chemoembolization (TACE) is the usual form.

Alpha particle helium-4 nucleus; a particles consisting of two protons and two neutrons bound together

Alpha particles, also called alpha ray 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. If the ion gains electrons from its environment, the alpha particle becomes a normal helium atom 4
2
He
.

References

  1. Tondreau, R. (1985). "Egas Moniz 1874–1955". Radiographics. 5 (6): 994–997. doi:10.1148/radiographics.5.6.3916824. PMID   3916824.
  2. "Archived copy" (PDF). Archived from the original (PDF) on 2011-07-16. Retrieved 2007-01-25.CS1 maint: archived copy as title (link)
  3. Kaick, Gerhard van; Andreas Dalheimer; Sakiko Hornik; Alexander Kaul; Dagmar Liebermann; Hertha Lührs; Andreas Spiethoff; Kurt Wegener; H. Wesch (1999-12-01). "The German Thorotrast Study: Recent Results and Assessment of Risks". Radiation Research . 152 (6): S64–S71. Bibcode:1999RadR..152S..64V. doi:10.2307/3580117. ISSN   0033-7587. JSTOR   3580117.
  4. Becker, N; D Liebermann; H Wesch; G Vankaick (June 2008). "Mortality among Thorotrast-exposed patients and an unexposed comparison group in the German Thorotrast study". European Journal of Cancer . 44 (9): 1259–1268. doi:10.1016/j.ejca.2008.02.050. ISSN   0959-8049. PMID   18395438 . Retrieved 2011-04-30.
  5. Bohatirchuk, F. P.; Jeletzky, T. F.; Ivan, L. P. (August 1973). "Contact historadiography of nervous tissue impregnated with thorotrast". Am J Roentgenol Radium Ther Nucl Med. 118 (4): 923–6. doi:10.2214/ajr.118.4.923. PMID   4593184.