Iodinated Organic Compounds As Contrast Media for Radiographic Diagnoses

Abstract

In the course of the experimental work leading to the development of pantopaque (ethyl iodophenylundecylate), it was observed that stable aqueous emulsions could be obtained easily with the medium (1, 2). Study of these emulsions has shown that they have the property of coating and adhering to mucosa and that they seem well adapted to the visualization of certain body cavities. In experimental examinations in dogs and other laboratory animals the most promising results have been obtained in bronchography, although satisfactory delineation may be produced in a number of other types of examination.2 Stable emulsions of ethyl iodophenylundecylate are formed when a 50 per cent mixture by volume with water containing up to 1 per cent of a surface active agent is passed numerous times through a colloid mill or other type of homogenizer. The surface active agents studied included bile salts, various neutral soaps, and a number of synthetics. Of these, oleyl methyl taurine (Igepon T gel) was found to be the most satisfactory when dissolved in the water phase at a concentration of 0.6 per cent. On standing, the emulsion prepared with Igepon T as a surface active agent separates into a lower milky phase, containing about 70 per cent of ethyl iodophenylundecylate, and a clear upper aqueous phase. The two phases are readily redispersed on shaking, and the resulting emulsion does not settle out for some hours. The two phases are easily separated by aspiration, or the emulsion may be diluted with isotonic saline. The size of the oil droplets in the emulsion varies somewhat with the mode of preparation, but usually they are of the order of 1.5–3.5 microns. Both the 50 and the 70 per cent emulsions may be readily injected through needles and catheters of small bore. As reported previously (2), ethyl iodophenylundecylate has a measurable toxicity in rats and mice which is consistent with the absorbability of the medium. The process of emulsification leads to an enormous increase in surface, and this in turn affects the values of the toxicity constants. The increase in surface does not alter significantly the ld 50 in mice as obtained by intraperitoneal injection, but does influence markedly the value found in rats. The intraperitoneal ld 50 of ethyl iodophenylundecylate has been reported to be 19 grams/kg. for 24-hour kill, while that of the emulsion has been found to be of the order of 2 grams/kg. It appears, on the basis of comparative work with other species, that the rat is particularly sensitive to ethyl iodophenylundecylate. Both ethyl iodophenylundecylate and its emulsion produce the same kind of pathological changes in the liver and kidneys of rats and mice when administered at or near the lethal level. Experimental Studies Bronchography: The spreading and coating properties of the emulsion were studied by making bronchograms in dogs. Other laboratory animals were briefly examined as experimental subjects but were found to be unsatisfactory.