Responsive contrast agents

Carrera, C., Digilio, G, Baroni, S., et al. (2007) Synthesis and characterization of a Gd(Ill) based contrast agent responsive to thiol containing compounds. Dalton Transactions, 4980-4987. 

Several metal ions play a crucial role in biological processes, whereas some others are toxic. Alteration of the metal concentration in the body can often be correlated to disease states. The necessity for in vivo determination of metal ion concentration and distribution has prompted research to develop appropriate metal-responsive MRI contrast agents. 

Aime et al. took advantage of the different redox states of manganese and of the difference in the related relaxation properties to design a p02 responsive contrast agent. The adducts formed between Mn /Mnn tpps complexes and poly-P-cyclodex-trin have considerably different relaxivities depending on the redox state of the metal, itself determined by the partial oxygen pressure of the solution (tpps — 5,10,15,20-tetrakis-(p-sulfonato-phenyl porphinate) (243). 

Toth E, Bolskar RD, Borel A, Gonzalez G, Flelm L, Merbach AE, Sitharaman B, Wilson LJ (2005) Water-soluble gadofullerenes Toward high-relaxivity, pFl-responsive MRI contrast agents. J. Am. Chem. Soc. 127 799-805. 

The rationale for this type of contrast agent is to use the endogenous metabolic pathway of lipid metabolism in the liver for the transport of iodinated substances. Chylomicron remnants are naturally occurring lipoproteins in the blood that are responsible for the transport of lipids into the liver. Three different mechanisms for this transport are discussed direct uptake by the low-density lipoprotein receptor transport to the low-density lipoprotein receptor-related protein (LRP) mediated by heparan sulfate proteoglycan (HSPG) or direct HSPG-LRP uptake and direct HSPG uptake. One of the prerequisites for particles to be transported by these mechanisms is a mean diameter of less than 100-300 run. 

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