Iodinated Organic Compounds As Contrast Media for Radiographic Diagnoses

Abstract

Apparently no serious attempt has been made to utilize iodinated organic compounds for the visualization of the gastro-intestinal tract. Iodized oils are used to a limited extent for specialized examinations, and there are occasional reports of experimental attempts to employ other iodinated compounds. To evaluate the possibilities of particulate iodinated organic compounds for gastro-intestinal work, tetraiodophthalimide (I), tetraiodophthalimidomethane (II), and tetraiodophthalimidoethanol (III) were synthesized and studied experimentally in dogs and to a limited extent clinically. It was soon apparent that the parent compound, tetraiodophthalimide, produced increased motility of the stomach. Although this effect may be useful for certain specialized problems, it does not appear to be a desirable quality for general use. Attention was then turned to tetraiodophthalimidoethanol. After some study it was found that this medium, when ground in water to a particle size of 1 to 2 microns, formed a suspension that had a number of desirable qualities. In comparison with barium sulfate suspensions, tetraiodophthalimidoethanol suspensions do not settle out as readily, are not so gritty, delineate more completely experimentally produced gastric lesions, adhere better to the bowel wall, and apparently do not inspissate so readily. Tetraiodophthalimidoethanol is a light yellow solid with a slightly greenish cast. The medium contains 73 per cent iodine and is considerably more opaque to x-rays than barium sulfate. The preparation of suitable aqueous suspensions on an experimental scale is a time-consuming process, since the product of chemical synthesis must be micronized in the dry state and then ground in a ball mill with water for several weeks. A properly prepared suspension is essentially non-settling at concentrations above 15 per cent by weight and becomes very thick at concentrations above 30 per cent. Studies on toxicity are still somewhat incomplete, but it appears that tetraiodophthalimidoethanol is of about the same order of toxicity as barium sulfate. Oral administration to fasting rats in doses up to 15 grams/kg. produced no toxic symptoms. Intraperitoneal injections in mice were productive of toxic manifestations at the range of 7.5 to 10 grams/kg. In comparison, barium sulfate suspensions when injected intraperitoneally in mice produced similar but less severe reactions at the same level of 7.5 to 10 grams/kg. Growth curves of rats raised on diets containing 4 per cent of added tetraiodophthalimidoethanol were more nearly normal than those obtained with 4 per cent added barium sulfate, but this may be due entirely to the effect of particle size, since the tetraiodophthalimidoethanol averaged about 10 microns, and the barium sulfate 1 to 2 microns. Experimental Studies Preparation of Suspensions: Tetraiodophthalimidoethanol as obtained by synthesis consisted of needles varying in particle size from 3 to 25 microns.