Clinical Contrast Agents

Generic name Chemical name/ brand name Acyclic (A)/ cyclic (C) Charge Hydration number Relaxivity r )l 

Gd(III) is the best candidate for application as an MRI CA because of its seven unpaired electrons and symmetric S-state, which is favorable for electron spins and results in a slow electronic relaxation rate. As a mid-member of the Ln family, Gd(III) has a coordination number of nine. In clinical CAs, chelates have a denticity of eight, and thus in Gd(III) occupy eight of the coordination sites, leaving the ninth for a coordinated water molecule. Gd(III) prefers hard donor atoms, such as N and O. The N and O of the carboxylate in DTPA and DOTA are coordinated to the metal center. The solid-state structure of Ln(III) DTPA was reported in 1984 [12], and that of Gd-DOTA was reported in 1993 [13], Gd(III) coordinates with 

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Figure 10.1 Clinical contrast agents with acyclic chelates.

Figure 10.2 Clinical contrast agents with cyclic chelates.

Table 10.1 Nomenclature, charge, hydration number, and relaxivity of clinical contrast agents.

Biomedical and Biotechnology. The use of mictocapsules for a variety of biomedical and biological appHcations has been promoted for many years (50,51). Several biomedical mictocapsule appHcations ate in clinical use or have approached clinical use. One appHcation is the use of air-fiUed human albumin mictocapsules as ultrasound contrast agents. Such mictocapsules, caUed mictobubbles, ate formed by ultrasonicating 5% albumin solutions to produce 4—10-)J.m diameter air-fiUed capsules (52). When injected the capsules act as a useful transpulmonary echo contrast agent (53) that has been approved for use in humans by the U.S. FDA. 

None of the products or experimental preparations is currently in clinical use or under development. Thorium oxide was not excreted at all furthermore it proved to be toxic because of long-lived a-radiation [4]. Other agents were not pursued because they displayed various types of toxicity or were less well tolerated than the extracellular contrast agents. Except thorium dioxide, none of them resulted in reliable and satisfactory contrast or provided important diagnostic information which could not have been obtained with a similar quality by more recently established imaging methods. In spite of an everlasting... 

CTP is a relatively recent development in acute stroke imaging that is already in routine clinical use in many centers. CTP and MRP are similar in that both techniques are based on rapid serial image acquisition during intravenous injection of a bolus of contrast material. In both techniques, measurements of density over time (for CTP) or signal intensity over time (for MRP) are converted to contrast agent-versus-time curves, and these are processed in similar ways to yield the same perfusion measurements (most often CBV, CBF, and MTT). Example CTP images are shown in Figure 2.12. 

Scheme 1. Ligands of the Gd111 complexes approved for clinical use as MRI contrast agents.

Fig. 12. X-ray crystal structure of complex 72, Na[Gd(DOTA)(H20)], an MRI contrast agent used clinically for detection of blood-brain barrier abnormalities. Adapted from (306).

Table 8.1 relaxivities of three clinically used Gd3+ chelate MRI contrast agents and selected water-soluble M C8, derivatives... 

Idee JM, Port M, Raynal I, Schaefer M, Le Greneur S, Corot C (2006) Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging a review. Fundam. Clin. Pharmacol. 20 563-576. 

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