THE CHEMISTRY OF IODINATED CONTRAST MEDIA

All the currently used contrast media are chemical modifications of a 2,4,6-triiodinated benzene ring. They are classified on the basis of their physical and chemical characteristics, including their chemical structure, osmolality, iodine content, and ionization in solution (2,3).

The parent molecule from which the contrast agents are derived is benzene. This is a toxic water-insoluble liquid. The carbon atoms on a benzene ring are numbered clockwise from 1 to 6. Benzoic acid is produced by introducing an acid group at position 1 on the benzene ring. This acid group permits the formation of salts or amides, which influence water solubility. 2,4,6-triiodobenzoic acid is obtained by introducing iodine atoms at positions 2, 4, and 6 on the ring. Iodine is the element used in contrast media as it possesses 3 important properties essential for the production of contrast media: high-contrast density, firm binding to the benzene molecule, and low toxicity. Triiodobenzoic acid is made less toxic and less lipophilic (fat-soluble) by introducing side chains at positions 3 and 5 (3).

OSMOLALITY, VISCOSITY, AND IONICITY

Because of their chemical properties, contrast media are usually thicker (viscosity) and have greater osmolality (more molecules per kilogram of water) than blood, plasma, or cerebrospinal fluid. Viscosity and osmolality play a part in the development of contrast reactions.

Ionicity is the characteristic of a molecule to break up into a positively charged cation and a negatively charged anion, resulting in more molecules per kilogram of water and thus increasing osmolality. Nonionic agents do not have this property and hence are less osmolar.

Ionic and nonionic contrast media may be monomeric or dimeric. Typically, 3 iodine atoms are delivered with each benzene ring of a contrast medium. If a contrast molecule contains only 1 benzene ring, it is called a monomer. To deliver more iodine with each molecule of contrast, 2 benzene rings may be combined to produce a dimer. This molecule would deliver 6 iodine atoms with each molecule.

In a solution, ionic monomers break up into their anion and cation components (increasing osmolality), delivering 3 iodine atoms (a 2:3 ratio of osmolar particles to iodine), whereas ionic dimers would deliver 2 ionic components per 6 iodine atoms (ratio, 1:3). Nonionic monomers do not break up in solution; a single molecule delivers 3 iodine atoms (ratio, 1:3), whereas a single nonionic dimer delivers 6 iodine atoms (ratio, 1:6). Thus, nonionic dimers are the most ideal contrast agents as they deliver the most iodine with the least effect on osmolality.

High-osmolality contrast media (HOCM) have 5–8 times the osmolality of plasma; low-osmolality contrast media (LOCM) have 2–3 times the osmolality of serum; and isoosmolar contrast media, which are increasingly used, have the same osmolality as blood, plasma, and cerebrospinal fluid.

The incidence of mild and moderate contrast reactions is higher for HOCM (6%–8%) than for LOCM (0.2%), but the incidence of severe reactions remains similar. Anaphylactoid reactions are more common while using HOCM, whereas cardiovascular decompensation is more common while using LOCM