Structural and relaxometric characterization of peptide aggregates containing gadolinium complexes as potential selective contrast agents in MRI.

The structural and relaxometric characterization of a novel class of supramol. aggregates, as potential tumor-specific contrast agents in magnetic resonance imaging (MRI), is reported. The aggregates are based on a new monomer with an upsilon shape (MonY) that contains, in the same mol., all three fundamental tasks that are required: a hydrophobic moiety that allows the formation of supramol. aggregates; the bioactive CCK8 peptide for target recognition; and a chelating agent able to give stable gadolinium complexes. As indicated by dynamic light scattering and small-angle neutron scattering (SANS) measurements, MonY and its gadolinium complex MonY(Gd) aggregate in aq. soln. to give ellipsoidal micelles with a ratio between the micellar axes of 1.7 and an aggregation no. Nagg of 30. There are no differences in the aggregation behavior of MonY and MonY(Gd), which indicates that the presence of metal ions, and therefore the redn. of the net charge, does not influence the aggregation behavior. When MonY or MonY(Gd) are blended with dioleoylphosphatidylcholine (DOPC), the aggregation behavior is dictated by the tendency of DOPC to give liposomes. Only when the amt. of MonY or MonY(Gd) is higher than 20 % is the coexistence of liposomes and micelles obsd. The thickness d of the bilayer is estd. by SANS to be 35-40 .ANG., whereas cryogenic TEM images show that the diam. of the liposomes ranges from 50 to 150 nm. Self-assembling micelles of MonY(Gd) present high relaxivity values (r1p = 15.03 mM-1 s-1) for each gadolinium complex in the aggregate. Liposomes contg. MonY(Gd) inserted in the DOPC bilayer at a molar ratio of 20:80 present slightly lower relaxivity values (r1p = 12.7 mM-1 s-1), independently of their internal or external position in the liposome