Paramagnetic chelate

The noncovalent approach is based on the use of complexes containing suitable moieties which are able to recognize specific proteins, primarily human serum albumin (HSA). When the targeting protein is confined in the blood, the adduct between the serum albumin and the functionalized complex may function as a blood pool agent. Due to the reversible nature of binding between the protein and the paramagnetic chelate, these adducts maintain excretory pathways typical of small complexes which, from the pharmacological point of view, favors them over covalently bound macromolecules. 

Dextrans are also attractive as macromolecular carriers of paramagnetic chelates because of their hydrophilicity, the different available molecular weights with narrow polydispersity, and the versatility of activation methods applicable. Several DTPA- or DOTA-loaded carboxymethyl dextran (CMD) derivatives have been prepared and tested in blood pool MRI.136-139 The relaxivities reported for these compounds are, however, relatively moderate. 

If the binding between the paramagnetic chelate, ML, and the protein, Prot, involves a single class of equivalent binding sites, the equilibrium is characterized by the association constant, ATa ... 

The efficiency of a paramagnetic chelate to act as a contrast agent is expressed by its proton relaxivity, ri or r2, referring to the paramagnetic enhancement of the longitudinal or transverse water proton relaxation rate, 1/T1 and 1/T2, respectively, by a unity concentration of the agent (ImM) ... 

Figure 4 Noncovalent interactions between (a) a hydrophobic side-chain of the ligand and a protein, and (b) a negatively charged paramagnetic chelate and a protein. In the first case, the protein-binding site is too far from the Gd + chelate to influence the water exchange, whereas in the second case, the exchange of the inner-sphere water is slowed down.

Paramagnetic chelates increase 1/Ti and I/T2 by approximately the same amount and are best visualized using Ti-weighted images. Gd " " is the lanthanide of choice for MRI owing to its symmetrical 5-state and slow electronic relaxation rate which is close to the frequency of protons in water. To avoid issues... 

Eu) the orientation can be turned through 90°. Using paramagnetic chelates, direct protein-lanthanide interactions can be abolished leading to better spectral resolution although some hysteresis effects due to molecular reorganization may complicate their use. 

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