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The Tragic History of Thorotrast

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The Tragic History of Thorotrast 2009 International Nuclear Atlantic Conference - INAC 2009 Rio de Janeiro,RJ, Brazil, September27 to October 2, 2009 ASSOCIAÇÃO BRASILEIRA DE ENERGIA NUCLEAR - ABEN ISBN: 978-85-99141-03-8 THE TRAGIC HISTORY OF THOROTRAST Ethel Mizrahy Cuperschmid 1 e Tarcisio Passos Ribeiro de Campos 2 1 Centro de Memória da Medicina Faculdade de Medicina – Universidade Federal de Minas Gerais Av.Alfredo Balena nº 190. Stª Efigênia. Belo Horizonte. 30130-100 [email protected] ou [email protected] 2Programa de Pós-Graduação em Ciências e Técnicas Nucleares Escola de Engenharia da Universidade Federal de Minas Gerais Av. Antônio Carlos nº 6627. PCA1 s.2285 Pampulha. Belo Horizonte 31270-901 [email protected] ABSTRAT Thorotrast, a colloidal solution of dioxide of natural thorium, slightly radioactive, had been applied on fluoroscopy applied since 1928 to the purpose of pielography, accomplishment for retrograde road, and to the contrast studies on the liver and on the spleen. The half-life of the thorium dioxide is 1,4 x 10 10 years. Its biological half-life can be taken from the International Commission on Radiological Protection (ICRP) as 8,000 days in bone, with, bone uptake of 70%; 700 days in the liver with 4% of liver uptake; 700 days in all other tissues and organs, in which 16% of uptake . The remaining 10% has been assumed to be excreted with a half- life of 0.5 days. Its Th-232 disintegration produces a series of radionuclides following a emission of alpha and beta particles ending on Pb208, a stable nuclide. However, the whole thorium dioxide is almost retained in the organism, keeping 70% deposited in the liver, 20% in the spleen and the remaining in the bony medulla and in the peripheral linfonodes. Thorotrast became the choice of the majority of the neurosurgerys at that time, as Egas Moniz, that rejected the sodium iodine at 25% concentration to adopt Thorotrast. That contrast had been used unrestrictly until 1950. The present article presents the medical discuss about Throtrast and investigates its oncology effects on human. 1. INTRODUCTION The radiological contrast namely Thorotrast began to be used in 1928, for Blühbaum, Frik and Kalkbrenner [1]. Thorotrast is a suspension that contains thorium dioxide particles, a radioactive material, whose chemical formula is ThO 2. It has been used as a radiological contrast in X-ray imaging since 1930 until 1950 decade. The thorium is a natural and abundant element. Its nuclide 232 Th is lightly unstable following a natural emission of an alpha particle. The thorium allows the production of suitable images due to its high opacity in radiography. It had been wide accepted by the radiologists due its excellence on contrasting internal human structures and due to its non acute collateral effect. It had been introduced on the market as Thorotrast in 1931 and had been provided 2 to 10 million exams. 2. DISCOVERY, APLICATION, REACTIONS Since 1931, the contrast had been used by Dr. Egas Moniz (1874-1955), winner of the Nobel Price of Physiology and Medicine at 1949. Egas Moniz contributed to the development of the medicine providing at first time the radiological visibility of the brain vascular system. Since 1927, brain angiographic had been investigated by Egas Moniz. He discovered after long experiences with X-rays the possibility of contrasting the vascular system on a radiological image. It turned possible to locate neoplasm aneurisms, hemorrhages and other abnormal formations in the human brain. Also, he had provided new ways for cerebral surgeries. That research was worth value to his indication to the Nobel Price; however, he received such commend together with other scientist Walter Rudolf Hess for the discovery of the therapeutic value of the pre-frontal leukotomia in the treatment of certain psychotic patients. Physicians Amandino Pinto and Almeida Lima, as well as Egas Moniz provided images of the brain vascular system by radiographic by means of Thorotrast. On that occasion, Egas Moniz concluded that Thorotrast is painless and it didn't provoke acute reaction in any tissues, however he identifies the long term uptake on same organs. In 1928, Egas Moniz came to Brazil for occasion of the Medical Days in Rio de Janeiro. On that occasion, he pronounced a lecture whose title was: "The arterial encephalographic in the diagnosis of brain tumors”. However, the contrast used in that period was the sodium iodated at 25% and it had not seemed to be the most appropriate one, because it had been provoked strong acute reactions in the patients. The clinical discoveries of Egas Moniz were recognized by a large number of neurologists of that time, whom had admired the sharpness of its analyses and observations. So the Thorotrast as soon it was developed had been spread on the medical field, being incorporated in the medical practices all around the world. Local reactions had happened, however, only when accidental injection occurred, for instance, in groin, in antecubit fossae and neck. On1932, the Pharmacy and North American Chemistry Councils expressed a warning in a publication in JAMA relating Thorotrax to the possible risk of a long term exposition to the radioactive thorium dioxide. Its use was considered unadvised on that time [2]. In 1936, Roussy, Oberling and Guérin had demonstrated the oncogenic effects of Thorotrast in rats, but they could not repeat the experiments in mouse [3]. In 1937 and 1938, the professor Luigi Bogliolo had investigated the cancer induction due to the radiological contrast in animal subjects. Bogliolo observed the appearance of sarcoma fusocelular fasciculano in mouse submitted to successive injections. The X-ray of one of the guinea pigs, obtained 78 days after the treatment end, revealed the presence of the contrast in the place of the injections [4][5]. The introduction of the contrast was made by direct i.v. injection. The drug was distributed in the liver, spleen, lymphatic nodes and bones, where it was absorbed. After this initial absorption, the slow redistribution of the product happened in long term. INAC 2009, Rio de Janeiro, RJ, Brazil. The biological half-life of thorium is estimated to be 22 years. It means that the patients' organs had been exposed to the alpha and beta radiation. Thus, Thorotrast was considered as carcinogenic. The physicians had been observed a high index of reincidence cancer in patients that made use of that contrast. Those tumors had usually appeared 20 to 30 years after injection. Thorotast had increased to 100% the risk of neoplasms if compared to the normal incidence in the population. The risk of leukemia had been increased 20 times. According to professor Luís Otavio Savassi Rocha (p.57), the most serious consequence of the use of Thorotrast was the late incidence of malign neoplams in the individuals exposed to the contrast. The publication of the first case of human malign tumor attributed to the Thorotrast exposition happened 19 years after its introduction in the medical practice. Besides the liver neoplasm cases, aplasic anemia, leukemia and an impressive incidence of chromosome aberrations were registered in exposed individuals [6]. 3.CONCLUSION The use of Thorotrast is a classic example of the iatrogenic. Its oncogenic potential had already been shown and checked in the 1930 decade, but it had been continued used even at 1954 in institutions of strong prestige in the medical area, such as Massachusetts General Hospital (of Boston), Laheyclinic (of Boston) and the University of Michigan Hospital (of Ann Arbor). Nowadays, iodinated hydrophilic molecules has been used universally as contrast agents for conventional X-ray, computer tomography and fluoroscopy procedures [7]. ACKNOWLEDGMENTS The authors acknowledge the CNPq, process n. 557805/2008-2 by financial aid and CT-saude process due to the help to the NRI-research group. REFERÊNCIAS 1. BLÜHBAUM, T.; FRIK, K & KALKBRENNER, H. “Eine neue Anwendungsart derKolloide in der Röntgendiagnostik”. Fortsch a. d. Geb. D. Röntgenstrahlen 37:18,1928. 2. Council on Pharmacy and Chemistry, JAMA. Thorotrat: preliminary report. Journal of American Medical Association , 99:2183, 1932. 3. ROUSSY, G.;OBERLING, C.H.; GURERIN, M. Ueber Sarkomerzeugung durch Kolloidales Thoriumdioxid Dei der Weisen Ratte. Strahlentherapie 56:160,1936. 4. BOGLIOLO, L. Produzione col thorotrast di um sarcoma fusocellulares fascicolato nel musculus var.alba. Pathologica 29:372, 1937. INAC 2009, Rio de Janeiro, RJ, Brazil. 5. BOGLIOLO, L. Sopra i blastomi sperimentali da ossido di tório. IIª Nota. Pathologica 30:422,1938. 6. ROCHA, Luiz Otávio Savassi. Vida e obra de Luigi Bogliolo . Belo Horizonte: Ed.Gráfica da Fundação Cultural de Belo Horizonte, 1992.521p. 7. SILPANANTA, Panee; ILLESCAS, Fernando F.; SHELDON, Huntington. Multiple Malignant neoplasms 40 years after angiography with Thorotrast. Canadian Medical Association Journal , vol 128, February, 1, 1983.p. 289-292. 8. http://www.sdirad.com , on 22 of june at 2009. INAC 2009, Rio de Janeiro, RJ, Brazil. .
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