High-relaxivity supramolecular aggregates containing peptides and Gd complexes as contrast agents in MRI.

Mixed supramol. aggregates, obtained by assembling together two amphiphilic monomers (C18H37)2NCO(CH2)2CO(AdOO)5-G-CCK8 (AdOO is 8-amino-3,6-dioxaoctanoic acid, CCK8 is C-terminal octapeptide of cholecystokinin) and (C18H37)2NCO(CH2)2COLys(DTPAGlu)CONH2 (DTPAGlu is N,N-bis[2-[bis(carboxyethyl)amino]ethyl]-L-glutamic acid), are characterized for their structural parameters by dynamic light scattering and for their relaxometric properties, in the absence and in the presence of 0.9 wt% NaCl. Two different aggregates (micelles and bilayer structures) are present in the absence of NaCl, while only bilayer structures are obsd. at physiol. ionic strength. The presence of NaCl increases the ionic strength, promoting a decrease in the repulsions between the polar heads and among the aggregates in soln., thus supporting the formation of large-curvature aggregates such as bilayer structures like vesicles. In these conditions the closed, vesicular shape and the large size (hydrodynamic radius of about 300 .ANG.) of the aggregates allow a high no. of paramagnetic gadolinium complexes and bioactive peptides to be accommodated on the inner and external surfaces. The presence of the salt causes a variation in the structural arrangement of the mols. and a partial rigidification of the assembled Gd(III) complexes on the surface vesicles, reducing their internal motions and giving an approx. 15% higher relaxivity value (r1p = 21.0 and 18.6 Mm-1 s-1 in the presence and in the absence of NaCl, resp.). The vesicles obtained, for the high relaxivity of each gadolinium complex and for the presence of a surface-exposed bioactive peptide, are very promising candidates as target-selective MRI contrast agents.