Agents sensitive to the redox potential

A diagnostic MRI probe sensitive to the in vivo redox potential would be very useful for detecting regions with a reduced oxygen partial pressure (PO2 ), a typical symptom of several pathologies including strokes.

Figure 28.8 pH dependence of the relaxivity (20 MHz, 25 °C) for the paramagnetic polymeric system reported in Figure 28.7

Very few Gd(III) chelates sensitive to the tissue oxygenation have been reported so far. Our group has investigated the potential ability of GdDOTP (DOTP = 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetrakis-methylenephosphonic acid) to act as an allosteric effector of haemoglobin.30 In fact, it has been observed that this chelate binds specifically to the T-form of the protein, which is characterized by a lower affinity towards oxygen. The interaction is driven by electrostatic forces and leads to a significant relaxivity enhancement (ca. 5-fold) owing to the restricted molecular tumbling of the paramagnetic complex once it is bound to the protein. Although haemoglobin can be considered as an excellent indirect target for detecting POl, the practical applicability of the method suffers from the inability of GdDOTP to enter red blood cells. Another approach deals with the use of liposomes built up with an amphiphilic Gd(III) complex containing a radical-sensitive disulphide bridge.31 The relaxivity (at 20 MHz and 25 ° C) of the liposomal paramagnetic agent is 13.6s_1mM_1, i.e. 2-fold higher than the free Gd(III) complex (r1 of 6.5s~1mM~1). Possibly, the limited relaxivity enhancement is due to the rotational flexibility of the complex bound to the liposome. This system was tested 'in vitro' by inducing the cleavage of the S—S bond chemically (by dithiothreitol) or physically (by 7-rays). In both cases the relaxivity decreased from the value of the liposomal agents to that of the free Gd(III) complex.

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