Thorotrast


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.
Thorium compounds produce excellent images because of thorium's high opacity to X-rays. 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. 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. 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.
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 after injection of Thorotrast. The risk of developing liver 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. 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.
Thorium is no longer used in X-ray contrast agents. Today, iodinated hydrophilic molecules are universally used as injected contrast agents in X-ray procedures.
The Danish director Nils Malmros's movie, Facing the Truth 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 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.