Thorotrast

Thorotrast bottle

Thorotrast is a suspension containing particles of the radioactive compound thorium dioxide, ThO₂, used as a contrast medium in X-ray diagnostics in the 1930s and 40s (use in some countries, such as the U.S., continued into the 1950s).

The naturally abundant thorium nuclide ²³²Th is slightly unstable and decays through the emission of an alpha particle. Thorium compounds produce excellent images because of thorium's high opacity to X-rays (it has a high cross section for absorption). 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. Two to 10 million patients worldwide have been treated with Thorotrast.

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 the alpha-radiation it emits for much of the rest of their lives. The significance of this exposure was not fully understood 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 (usually 20-30) after injection of Thorotrast. The risk of getting 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. These observations have led some to characterize Thorotrast as the most potent known human carcinogen.

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. Today, iodinated hydrophilic molecules are universally used as contrast agents for X-ray procedures.

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

References

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