5-[3-Hydroxy-2-hydroxymethyl-propionamido)- N, N'-dimethyl- N, N'-bis-(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

Kenneth T. Cheng

PMID: 20641966

Abstract:

5-[3-Hydroxy-2-hydroxymethyl-propionamido)-N,N´-dimethyl-N,N´-bis-(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (iobitridol) 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).
As a low-osmolar nonionic monomer, iobitridol was developed in an effort to increase the safety and tolerance of X-ray contrast agents. The development of iobitridol was based on the belief that shielding of the hydrophobic areas of the 1,3,5-triiodobenzene ring from interaction with biological sites in vivo would decrease the chemotoxicity of this class of compounds (10-12). This compound is characterized by the introduction of a methyl group as second substituent in the tertiary amido group of the benzamide substituent chains to decrease the flexibility of the polar side-chains and to stabilize the hydrophilic sphere. However, Violon (13) compared iobitridol with four other nonionic monomers based on semi-empirical quantum mechanical calculations alone and concluded that the structured did not seem to stabilize the hydrophilic sphere to a greater extent than other studied molecules. Iobitridol is not commercially available in the United States but is available (250-350 mg iodine(I)/ml) in Europe for angiography, venography, and computed tomography (CT) examinations.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2012319	2,4,6-Triiodobenzoic acid		2012-31-9	Price