Nonionic contrast agents

Fig. 6. Route of synthesis of nonionic contrast agents, a Synthesis of iohexol with a symmetrical structure. R = R = 2,3-propandiol.b Synthesis of iopromide with an unsymmetrical structure. Ri = methyl. R2 = 2,3-propandiol. R2=acylated 2,3-propandiol...

The use of complexed Gd + in MRI relies on the high stability of the Gd-DTPA complex to maintain an extremely low level of free Gd +, but some side-effects have been observed using such ionic compounds, prompting current research to produce nonionic contrast agents. 

Cohen MD. A review of the toxicity of nonionic contrast agents in children. Invest Radiol 1993 28(Suppl 5) S87-93. 

The synthesis of iodinated ionic and nonionic contrast agents follows a general pattern, which includes (1) the selection and synthesis of an intermediate containing the ring nucleus, (2) introduction of an activating group, (3) iodination, and (4) acylation. 

More synthetic steps and more different intermediates are required to complete the synthesis of nonionic contrast agents than that of ionic contrast agents. The commonly used intermediates for introducing (poly)hydro al-kyl groups to the triiodophenyl ring in a nonionic contrast molecule are amino-alco-... 

One of the methods for synthesis of iohexol (7b), a nonionic contrast agent, is shown in equation (10.5) (246). Nonionic contrast media are more costly to manufacture than are ionic constrast media. The cost of nonionic contrast media is determined by the number of synthetic steps, overall yield, cost of the intermediates, difficulties in isolation and purification, and other associated manipulations. Many alternate paths of synthesis and purification of nonionic contrast agents have been reported. For example, the nonionic contrast agent ioxilan (7j) can alternately be prepared... 

In designing improved nonionic contrast agents, high water solubility is achieved by masking and shielding the lipophilic regions of... 

Nonionic contrast agents are less anticoagulant than ionic contrast agents (402-405). Ranganathan et al. (313, 314) showed that placing a heterocyclic ring substituent in the 5-position of the 2,4,6-triiodo-l,3-benzenedi-carboxamide moiety can confer an unexpected anticoagulant behavior to the nonionic contrast molecule. 

The cost differential between ionic and nonionic contrast agents is substantial and is a consideration for cost containment in health maintenance. In 1994 in the United States this cost differential is estimated to be about 10- to 20-fold, and it is far smaller in Europe (852). The cost differential between nonionics and ionics has been reduced to 5 or 6 to 1 in 2002 in the United States, according to one of the reviewers of this manuscript. This reviewer also indicated that ionic contrast media are no longer administered intravenously, but used instead to fill lumens (i.e., bladders, fistulas, etc.). 

Note. Recently nonionic contrast agents are commonly used in radiological studies. Preparations of various concentrations are in the market. 

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