Thorotrast is a

suspension Suspension or suspended may refer to: Science and engineering * Suspension (topology), in mathematics * Suspension (dynamical systems), in mathematics * Suspension of a ring, in mathematics * Suspension (chemistry), small solid particles suspend ...

containing particles of the

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 consid ...

compound

thorium dioxide Thorium dioxide (ThO2), also called thorium(IV) oxide, is a crystalline solid, often white or yellow in colour. Also known as thoria, it is produced mainly as a by-product of lanthanide and uranium production. Thorianite is the name of the minera ...

, ThO₂; it was used as a

radiocontrast agent Radiocontrast agents are substances used to enhance the visibility of internal structures in X-ray-based imaging techniques such as computed tomography (contrast CT), projectional radiography, and fluoroscopy. Radiocontrast agents are typically io ...

in clinical

radiography Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical radiography ("diagnostic" and "therapeut ...

in the 1930s to 1950s. It is no longer used clinically.

Thorium Thorium is a weakly radioactive metallic chemical element with the symbol Th and atomic number 90. Thorium is silvery and tarnishes black when it is exposed to air, forming thorium dioxide; it is moderately soft and malleable and has a high me ...

compounds produce excellent images because of thorium's high opacity to X-rays (it has a high

cross section Cross section may refer to: * Cross section (geometry) ** Cross-sectional views in architecture & engineering 3D *Cross section (geology) * Cross section (electronics) * Radar cross section, measure of detectability * Cross section (physics) **Abs ...

for absorption). However, thorium is retained in the body, and it is radioactive, emitting harmful

alpha radiation 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 atom ...

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 António Caetano de Abreu Freire Egas Moniz (29 November 1874 – 13 December 1955), 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, ...

contributed to its development. 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 The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

s, and

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

, where it is absorbed. After this initial absorption, redistribution takes place at a very slow pace. Specifically, the

biological half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

is estimated to be 22 years. 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. 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 Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...

(or

bile duct cancer 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 ...

) 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 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 ' ...

appears to be 20 times higher in Thorotrast patients. Thorotrast exposure has also been associated with the development of

angiosarcoma 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 ...

. German patients exposed to Thorotrast had their median life-expectancy shortened by 14 years in comparison to a similar non-exposed control group. Thorium is no longer used in X-ray contrast agents for clinical use. Today, iodinated hydrophilic (water-soluble) molecules are universally used as injected contrast agents in clinical X-ray procedures. The

Danish Danish may refer to: * Something of, from, or related to the country of Denmark People * A national or citizen of Denmark, also called a "Dane," see Demographics of Denmark * Culture of Denmark * Danish people or Danes, people with a Danish a ...

director

Nils Malmros Nils Malmros (born 1944), a Danish film director and screenwriter, is considered a leading auteur of realism in Danish cinema.Nissen, Dan, ''Malmros, Nils'', International Dictionary of Films and Filmmakers, Gale Group, (2001) retrieved 2 August ...

's movie, '' Facing the Truth'' (original

title ''At Kende Sandheden'') from 2002, portrays the dilemma that faced Malmros's father,

Richard Malmros Richard is a male given name. It originates, via Old French, from Old Frankish and is a compound of the words descending from Proto-Germanic ''*rīk-'' 'ruler, leader, king' and ''*hardu-'' 'strong, brave, hardy', and it therefore means 'stron ...

, 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 World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...

. The use of Thorotrast in Denmark ended in 1947 when safer alternatives became available.

Current use

In the decades after the cessation of its clinical use, Thorotrast has sometimes been used in laboratory research to stain neural tissue samples for examination by

historadiography 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 ...

References

{{Contrast media Hepatotoxins IARC Group 1 carcinogens Health disasters Thorium Withdrawn drugs Radiocontrast agents