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thorium dioxide

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.)

Thorium compounds produce excellent images because of thorium's high opacity to X-rays (it has a high cross section for absorption). Unfortunately, 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 and angiosarcomas 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.

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]

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 injected contrast agents for X-ray procedures.

Current use

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

References

^ Tondreau, R. (1985). "Egas Moniz 1874-1955". Radiographics 5 (6): 994–997. doi:10.1148/radiographics.5.6.3916824. PMID 3916824.
^ http://www.ead.anl.gov/pub/doc/thorium.pdf
^ 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. doi:10.2307/3580117. ISSN 0033-7587. JSTOR 3580117.
^ 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. Retrieved 2011-04-30.
^ "Contact historadiography of nervous tissue impregnated with thorotrast". Am J Roentgenol Radium Ther Nucl Med 118 (4): 923–6. August 1973. PMID 4593184.

UpToDate Contents

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1. 悪性肝腫瘍の病理pathology of malignant liver tumors [show details]
…It can be caused by exposure to vinyl chloride , arsenic, anabolic steroids, radiation, and thorium dioxide. Patients typically present with abdominal pain, fatigue, jaundice, ascites, and weight loss…
2. 原発性骨髄線維症における病態pathogenetic mechanisms in primary myelofibrosis [show details]
…postulated for PMF . The occurrence of PMF has, in a minority of cases, been linked to exposure to thorium dioxide, petroleum manufacturing plants (especially toluene and benzene), and ionizing radiation . A…
3. 胆管癌の疫学、病因、および分類epidemiology pathogenesis and classification of cholangiocarcinoma [show details]
…transplantation compared with those who did not undergo transplantation . Thorotrast – A clear association exists between exposure to Thorotrast (a radiologic contrast agent banned in the 1960s for its carcinogenic…
4. 悪性腹膜中皮腫：疫学、危険因子、臨床所見、診断、および病期分類malignant peritoneal mesothelioma epidemiology risk factors clinical presentation diagnosis and staging [show details]
…pleural mesothelioma . MPM has been reported in three separate cohorts of patients who received thorotrast for radiological examinations . The cumulative incidence of MPM in these series is 0.2 to 0.6 percent…
5. 悪性胸膜中皮腫の疫学epidemiology of malignant pleural mesothelioma [show details]
…risk . In rare cases malignant pleural mesothelioma has been associated with intrapleural thorium dioxide (Thorotrast), a radioactive contrast agent in the 1930s and 1940s . Carbon nanotubes share similar…

English Journal

Radioactive characterization of the main materials involved in the titanium dioxide production process and their environmental radiological impact.

Mantero J, Gazquez MJ, Bolivar JP, Garcia-Tenorio R, Vaca F.SourceGrupo Física Nuclear Aplicada, Departamento Física Aplicada II, Universidad de Sevilla, E.T.S.A., Avenida Reina Mercedes, 241012 Sevilla, Spain.
Journal of environmental radioactivity.J Environ Radioact.2013 Jun;120:26-32. doi: 10.1016/j.jenvrad.2013.01.002. Epub 2013 Feb 12.
A study about the distribution of several radionuclides from the uranium and the thorium series radionuclides along the production process of a typical NORM industry devoted to the production of titanium dioxide has been performed. With this end the activity concentrations in raw materials, final pr
PMID 23416226

Incidental hyperdensities within the reticuloendothelial system.

Amirbekian S, Ibrahim SM, Shin MS.SourceDepartment of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520-8042, USA. Electronic address: smbat.amirbekian@yale.edu.
Clinical imaging.Clin Imaging.2013 May-Jun;37(3):583-5. doi: 10.1016/j.clinimag.2012.09.001. Epub 2013 Jan 10.
This is a case report of a 79-year-old woman who was found to have numerous hyperdense nodular lesions in the upper abdomen, which were incidentally discovered during routine follow-up of a lung nodule. These hyperdense lesions included a lace-like reticular distribution within the liver, multiple e
PMID 23313189

Japanese Journal

Histological type of Thorotrast-induced liver tumors associated with the translocation of deposited radionuclides

YAMAMOTO Yoichiro,CHIKAWA Junichi,UEGAKI Yoshinobu,USUDA Nobuteru,KUWAHARA Yoshikazu,FUKUMOTO Manabu
Cancer science 101(2), 336-340, 2010-02-10
NAID 10026587581

非ウイルス性肝発癌要因放射線被ばくによる肝発がん--トロトラスト症発がん機構解明の温故知新 (肝癌--基礎・臨床研究のアップデート) -- (肝癌の発生・進展機序)

福本学,桑原義和
日本臨床 67(-) (956), 156-160, 2009-05
NAID 40016676280

Gene expression profiles in mouse liver cells after exposure to different types of radiation

Roudkenar Mehryar Habibi,Li Li,Baba Taisuke [他],KUWAHARA Yoshikazu,NAKAGAWA Hironobu,WANG Lu,KASAOKA Satoshi,OHKUBO Yasuhito,ONO Koji,FUKUMOTO Manabu
Journal of radiation research 49(1), 29-40, 2008-01-15
… In order to elucidate radiation-induced liver cancers including Thorotrast, we present a new approach to investigate in vivo effects of internal exposure to α-particles. …
NAID 110006570525

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