Contrast agents, nonspecific

Molecular and cellular processes were visualized by X-ray contrast agents long before the term molecular imaging became popular and even before the advent of early CT (Table 1). Because of the above-mentioned limitations in the sensitivity of contrast detection by X-ray radiography, the latter can only visualize high capacity transport mechanisms and the nonspecific uptake of particles by specialized cells. 

In 1998, the commercial introduction of multislice computed tomography made X-ray functional imaging possible. Specific contrast agents that could remain within the intravascular compartment for a substantially longer time than conventional nonspecific agents may allow the quantification of local blood volume, tissue perfusion and permeability and thus the characterization of several types of lesions. 

Fig. 1. Schematic compartmental pharmacokinetic representation of different classes of contrast agents a. nonspecific agent (NSA e.g. iobitridol) b. low-diffusion agent (LDA) c. rapid-clearance blood-pool agent (RCBPA e.g. P743) d. slow-clearance blood-pool agent (SCBPA, e.g. P840). From Id e et al. (2001) Invest Radiol 26 41,with permission ( Lippincott Williams Wilkins)...

Ba-Ssalamah A, Schima W, Schmook MT, et al (2002) Atypical focal nodular hyperplasia of the liver imaging features of nonspecific and liver-specific MR contrast agents. AJR Am J Roentgenol 179 1447-1456... 

Complex Ion Formation. Phosphates form water-soluble complex ions with metallic cations, a phenomenon commonly called sequestration. In contrast to many complexing agents, polyphosphates are nonspecific and form soluble, charged complexes with virtually all metallic cations. Alkali metals are weakly complexed, but alkaline-earth and transition metals form more strongly associated complexes (eg, eq. 16). Quaternary ammonium ions are complexed Htde if at all because of their low charge density. The amount of metal ion that can be sequestered by polyphosphates generally increases... 

In contrast, much recent evidence suggests that these supposedly nonspecific agents might act by binding directly to a particularly sensitive protein, rather than a phospholipid membrane, as target (Franks and Lieb,... 

The nonspecific membrane actions of local anesthetics can be easily ruled out, because most clinically useful agents, in contrast to general anesthetics, possess a defined set of structure-activity relationships. As mentioned earlier, local anesthetic agents block nerve conductance and produce anesthesia as a result of their selective actions on membrane-bound sodium channels. It should be pointed out that at much higher drug concentrations, local anesthetics also bind and block potassium channels. 

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