History of the use and toxicity of thorotrast.

In Lisbon, Professor Egaz Moniz, Nobel Prize laureate in medicine for 1945, pioneered the introduction and use of Thorotrast particularly for the visualization of arteries. He produced a large number of excellent publications which contributed, within 2 to 3 years of its first production, to its widespread adoption throughout Europe, Japan and North America. Moniz was not alone in this pioneer work. Thorotrast proved to be an excellent contrast agent and within a few years, was rapidly adopted both for systemic and local use by injection or instillation into virtually every orifice and cavity in the body. Its prime use was as a contrast agent for systemic use for arteriography and venography. The predecessor of Thorotrast under the name “Umbrathor” was introduced as a radiological contrast agent in Germany by the firm of Heyden in the late 1920s. This material was not suitable for systemic injection. In the late 192Os, Moabit Heyden, at the suggestion of Berlin University, worked with a variety of preparations of Thorotrast sol. The object of this work was to produce an alkahne-stable form of thorium dioxide solution which would not flocculate with body fluids. This was eventually achieved and the product produced and marketed under the trade name of Thorotrast in 1931. Thorotrast proved to be an ideal radiographic agent for use in demonstrating cavities and narrow canals. Futhermore, it could also be administered both intravenously and intra-arterially. Excellent X-rays of the liver, spleen, ducts and vessels (hepatosplenography) were obtained after systemic intravenous injection. After arterial administration, outstanding pictures of the brain (arterial encephalography) and also of the arteries of the limbs were obtained. In numerous publications, the excellent clarity of the pictures was emphasized, as well as the painlessness of administration (12, 13, 15, 16). Thorotrast was used for local and systemic injections. The standard amounts employed, in precise terms, remain largely unknown. There was, however, a degree of consistency in the amount used for the more common types of similar investigations. Cerebral angiography usually involved between 20 and 50 ml of Thorotrast being injected into the carotid artery. Limb angiography involved perhaps 20 ml injected into the appropriate blood vessels. The hepatosplenography and lienography tended to involve 50 to 70 ml of Thorotrast. In contrast, perinasal sinus visualization involved the instillation of 2 to 5 ml of Thorotrast directly into the nasal sinuses. The amount used for other sinus and abscess locali-