Hydrophilic contrast agents

The earliest and most widely studied particulate carriers for paramagnetic substances are the liposomes, either entrapping hydrophilic contrast agents within the internal aqueous phase, or incorporating lipophilic complexes in their phospholipidic bilayer membrane 100,101). 

Figure 1 Schematic structures of micelle and liposome, their formation and loading with a contrast agent, (a) A micelle is formed spontaneously in aqueous media from an amphiphilic compound (1) that consists of distinct hydrophilic (2) and hydrophobic (3) moieties. Hydrophobic moieties form the micelle core (4). Contrast agent (asterisk gamma- or MR-active metal-loaded chelating group, or heavy element, such as iodine or bromine) can be directly coupled to the hydrophobic moiety within the micelle core (5), or incorporated into the micelle as an individual monomeric (6) or polymeric (7) amphiphilic unit, (b) A liposome can be prepared from individual phospholipid molecules (1) that consists of a bilayered membrane (2) and internal aqueous compartment (3). Contrast agent (asterisk) can be entrapped in the inner water space of the liposome as a soluble entity (4) or incorporated into the liposome membrane as a part of monomeric (5) or polymeric (6) amphiphilic unit (similar to that in case of micelle). Additionally, liposomes can be sterically protected by amphiphilic derivatization with PEG or PEG-like polymer (7) [1].

More recently, micelles have also been proposed as contrast agents. They are colloidal particles with a hydrophobic core and a hydrophilic shell, formed by amphiphilic compounds 102). 

Most contrast agents elicit nephrotoxicity because they are primarily excreted by the kidneys. However, when administered in small doses, they constitute a rich source of GFR markers. The two major classes of contrast agents that are finding clinical utility as GFR markers are iodinated aromatic compounds and metal complexes. lodinated aromatics such as iohexol and iothalamate (Fig. 13) are commonly used as contrast agents for computed tomography (GT). They also have pharmacokinetics similar to inulin and hence are useful indicators of renal status [215]. The iodinated molecules used for GFR measurements consist of a triiodo-benzene core and hydrophilic groups to enhance solubility in aqueous medium. 

Hydrophilicity, osmolahty and viscosity are directly related to the chemical structure of the contrast agents. 

The partition coefficients of non-ionic monomeric contrast agents in the system water/n-butanol are in the range 0.03-0.15. Dimers are more hydrophilic, e.g. with a P value of 0.005 for iotrolan (Table 2). 

Structural features such as electrical charge, hydroxyl groups in the side-chains and amino atoms of the amide groups reduce the lipophilicity (increase the hydrophilicity) whereas additional methyl groups sitting on amino moieties or free positions on the benzene ring increase the fipophilicity. Biliary contrast agents with a free position have > 5. 

Fig. 7. Comparison of the two different types of extracellular and biliary contrast agents. One monomeric and one dimeric example are illustrated from each type, lopromide and iotrolan (extracellular type) are extremely hydrophilic whereas iopodinic acid and iotroxic acid (biliary type) are both ionic and very lipophilic... 

Figures 8 and 9 summarize other structural types of monomeric and dimeric hepatospecific X-ray contrast agents. All monomeric compounds are characterized by a free 4-position, by one negative charge in the form of a carboxyl group and by substituents lacking hydrophilic moieties such as hydroxyl groups. Two of the dimeric substances also have free 4-positions, one, iosefamate, has a...

Licha K, Riefke B, Ntziachristos V, Becker A, Chance B, Semmler W (2000) Hydrophilic cyanine dyes as contrast agents for near-infrared tiunor imaging synthe-... 

These contrast agents are all non-specific, even if their distribution in the body is far from homogeneous. Indeed, their efficacy in enhancing contrast stems only from their preferential distribution in the blood stream because they are all quite hydrophilic. There thus remains the need for new compounds of improved performances. Increased efficacy, exclusive blood distribution, target-... 

Soderlind et al. (2008) reported ultrasmall perovskite GdFeOs NCs (around 4 nm) via a polyol route. The small size and hydrophilic surface suggests potential application as contrast agents in bioimaging. 

Intravascular contrast agents should have low viscosity and low osmolality as close as possible to those of body fluids, to improve tolerance and minimize adverse reactions. Contrast agents intended for oral cholecystography should possess hydrophilic and lipophilic properties, so that the compoundcan be orally absorbed, should be excreted from the liver and bile ducts in sufficient amount to provide radiopacity, and should have no adverse side effects. Because each of these properties is associated with certain molecular features and not all of them are structurally compatible, the best radiopaques represent a compromise of a maximum of these desirable qualities. 

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