,´-Bis(2,3-dihydroxypropyl)-5-[-(2-hydroxyethyl-3-methoxypropyl)-acetamidol]-2,4,6-triiodoisophthalamide

,´-Bis(2,3-dihydroxypropyl)-5-[-(2-hydroxyethyl-3-methoxypropyl)-acetamidol]-2,4,6-triiodoisophthalamide (iopentol) is a nonionic X-ray contrast agent used in various radiologic procedures to aid the radiographic visualization of selected tissues or organs. X-Ray imaging (planar and tomographic) techniques depend on tissue density differences that provide the image contrast produced by X-ray attenuation between the area of interest and surrounding tissues (1, 2). Contrast enhancement (opacification) with use of contrast agents increases the degree of contrast and improves the differentiation of pathologic processes from normal tissues. Because iodine, an element of high atomic density, causes high attenuation of X-rays within the diagnostic energy spectrum, water-soluble and reasonably safe iodinated contrast agents in intravenous injectable forms have been developed for clinical applications (3, 4). Water-soluble, intravenous X-ray contrast agents are generally organic iodine compounds that contain one or more tri-iodinated benzene rings (5, 6). When injected intravenously, they are largely distributed in the extracellular fluid space and excreted unchanged by the kidneys (7). Contrast enhancement of a region of interest depends on the route of administration, delivery of the agent to the area by blood flow, and the final iodine concentration in the region. There are two basic types of these compounds: ionic and nonionic agents. The first monomeric ionic compound, in the form of 2,4,6-triiodobenzene acetrizoic acid, was synthesized by Wallingford (3). Most ionic contrast agents are derived from the basic structures of 3,5-diamino-2,4,6-triiodobenzoic acid, 5-amino-2,4,5-triiodoisophthalic acid, or 2,4,6-triiodobenzene-1,3,5-tricarbonic acid. In addition to monoacidic ionic dimers, nonionic compounds have also been developed to improve the tolerability of these agents in patients. The basic strategy of developing nonionic agents is to eliminate the electrical charges in the structure, which will lead to a reduction in osmolality of the compound. Because osmolality is related to the number of particles in solution, the challenge is to reduce the number of particles but maintain the iodine concentration (8). This was generally achieved by conversion of the carboxyl groups to hydroxyalkylamide groups (9). Further improvement was made by replacing the amino sugar with aminoalcohols to produce heat-stable hydroxyalkylamides to allow product sterilization (10). As a low-osmolar nonionic monomer, iopentol was developed in an effort to increase the safety and tolerance of X-ray contrast agents. Chemically, it is a -carboxamido--iodo--(β-hydroxyalkyl)aniline derivative and a water-soluble ratio 3.0 (3 iodine atoms to 1 osmotic particle) compound (11, 12). Iopentol is not commercially available in the United States. It has been used in Europe for arteriography, urography, phlebography and computed tomography enhancement, arthrography, endoscopic retrograde cholangiopancreatography, hysterosalpingography, and gastrointestinal studies. The commercial preparations were available in iodine concentrations ranging from 150 to 350 mg/ml (13).