Thorotrast

Last updated
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.

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.

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.

Thorotrast was used in Portugal from 1930 to 1955. Epidemiological studies from Portugal showed a link between Thorotrast use and risk of developing leukaemia was significant and went so far as describing it as the most potent leukaemogen reported. They also noted very high levels of haemangioendotheliomas normally of the liver and they were very rarely seen in controls. [3]

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. [4] 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. [5]

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.

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.

Current use

Thorotrast has also been used in research to stain neural tissue samples for examination by historadiography. [6]

Related Research Articles

Actinium Chemical element, symbol Ac and atomic number 89

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 group of 15 similar 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.

Polonium Chemical element, symbol Po and atomic number 84

Polonium is a chemical element with the symbol Po and atomic number 84. Polonium is a chalcogen. A rare and highly radioactive metal with no stable isotopes, polonium is 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 slightly longer-lived isotopes exist, 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.

Radon Chemical element, symbol Rn and 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 it one of the rarest elements. Since thorium and uranium are two of the most common radioactive elements on Earth, while also having three isotopes with half-lives on the order of several billion years, radon will be present on Earth long into the future despite its short half-life. The decay of radon produces many other short-lived nuclides, known as radon daughters, ending at stable isotopes of lead.

Soft-tissue sarcoma Medical condition

A soft-tissue sarcoma(STS) is a malignant tumour, a type of cancer, that develops in soft tissue. A soft tissue sarcoma is often a painless mass that grows slowly over months or years. They may be superficial or deep-seated. Any such unexplained mass must be diagnosed by biopsy. Treatment may include, surgery, radiotherapy, chemotherapy, and targeted drug therapy. The other type of sarcoma is a bone sarcoma.

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.

Nuclear medicine Medical specialty

Nuclear medicine is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear medicine imaging, in a sense, is "radiology done inside out" or "endoradiology" because it records radiation emitting from within the body rather than radiation that is generated by external sources like X-rays. In addition, nuclear medicine scans differ from radiology, as the emphasis is not on imaging anatomy, but on the function. For such reason, it is called a physiological imaging modality. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) scans are the two most common imaging modalities in nuclear medicine.

António Egas Moniz Portuguese neurologist (1874–1955)

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—​better known today as lobotomy—​for which he became the first Portuguese national to receive a Nobel Prize in 1949.

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.

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 sulfate. The contrast agents 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.

Historadiography is a technique formerly utilized in the fields of histology and cellular biology to provide semiquantitative information regarding the density of a tissue sample. It is usually synonymous with microradiography. This is achieved by layering a ground section of mineralized tissue with photographic emulsion on a glass slide and exposing the sample to a beam of X-rays. After developing the emulsion, the resulting radiograph can be viewed with a microscope. A side-by-side comparison with a slide containing radiographs of various substances of known mass can provide a rough mass estimate, and therefore a rough approximation of the concentration of calcium salts in the sample.

Cholangiocarcinoma Bile duct adenocarcinoma

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.

Angiosarcoma Cancer of the lining of the blood or lymphatic vessels

Angiosarcoma is a rare and aggressive cancer that starts in the endothelial cells that line the walls of blood vessels or lymphatic vessels. Since they are made from vascular lining, they can appear anywhere and at any age, but older people are more commonly affected, and the skin is the most affected area, with approximately 60% of cases being cutaneous. Specifically, the scalp makes up ~50% of angiosarcoma cases, but this is still <0.1% of all head and neck tumors. Since angiosarcoma is an umbrella term for many types of tumor that vary greatly in origin and location, many symptoms may occur, from completely asymptomatic to non-specific symptoms like skin lesions, ulceration, shortness of breath and abdominal pain. Multiple-organ involvement at time of diagnosis is common and makes it difficult to ascertain origin and how to treat it.

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.

Linear no-threshold model Deprecated model predicting health effects of radiation

The linear no-threshold model (LNT) is a dose-response model used in radiation protection to estimate stochastic health effects such as radiation-induced cancer, genetic mutations and teratogenic effects on the human body due to exposure to ionizing radiation. The model statistically extrapolates effects of radiation from very high doses into very low doses, where no biological effects are observed. The LNT model lies at a foundation of a postulate that all exposure to ionizing radiation is harmful, regardless of how low the dose is, and that the effect is cumulative over lifetime. The model ignores existing DNA repair mechanisms and is not supported by biological evidence and deprecated by international bodies specializing in radiation protection.

Actinides in the environment

Environmental radioactivity is not limited solely to actinides; non-actinides such as radon and radium are of note. While all actinides are radioactive, there are a lot of actinides or actinide-relating minerals in the Earth's crust such as uranium and thorium. These minerals are helpful in many ways, such as carbon-dating, most detectors, X-rays, and more.

<i>Facing the Truth</i> (film) 2002 film

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.

Liver cancer Medical condition

Liver cancer is cancer that starts in the liver. Liver cancer can be primary or secondary. Liver metastasis is more common than that which starts in the liver. Liver cancer is increasing globally.

Alpha particle Helium-4 nucleus; particle of two protons and two neutrons

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
.

Exposure to ionizing radiation is known to increase the future incidence of cancer, particularly leukemia. The mechanism by which this occurs is well understood, but quantitative models predicting the level of risk remain controversial. The most widely accepted model posits that the incidence of cancers due to ionizing radiation increases linearly with effective radiation dose at a rate of 5.5% per sievert; if correct, natural background radiation is the most hazardous source of radiation to general public health, followed by medical imaging as a close second. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by ultraviolet radiation. Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been described as a possible carcinogen by the WHO's International Agency for Research on Cancer, but the link remains unproven.

Liver angiosarcoma Medical condition

Liver angiosarcoma also known as angiosarcoma of the liver or hepatic angiosarcoma is a rare and rapidly fatal cancer arising from endothelial that line the blood vessels of the liver. It is a type of angiosarcoma. Although very rare with around 200 cases diagnosed each year, it is still considered the third most common primary liver cancer, making up around 2% of all primary liver cancers. Liver angiosarcoma can be primary, meaning it arose in the liver, or secondary, meaning the angiosarcoma arose elsewhere and metastasized to the liver. This article covers PHA, however much is also applicable to secondary tumors.

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. Silva Horta, J.; Abbatt, John D.; Motta, L. Cayolla; Tavares, M. Helena (July 1972). "Leukaemia, malignancies and other late effects following administration of Thorotrast". Zeitschrift für Krebsforschung und Klinische Onkologie. 77 (3): 202–216. doi:10.1007/BF02570686. ISSN   0084-5353.
  4. 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. PMID   10564940.
  5. 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.
  6. 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.