Micelles derivatized with octreotide as potential target-selective contrast agents in MRI.

New amphiphilic monomers (OCA-DTPAGlu and OCA-DOTA) containing, in the same molecule, three different functions: (i) the chelating agent (DTPAGlu or DOTA) able to coordinate gadolinium ion, (ii) the octreotide bioactive peptide able to target somatostatin receptors, and (iii) a hydrophobic moiety with two 18-carbon atoms alkyl chains have been designed and synthesized by solid-phase methods. The novel amphiphilic monomers aggregate, in water solution, giving stable micelles at very low concentration (cmc values of 2.3 x 10(-6) mol kg(-1) and 2.5 x 10(-6) mol kg(-1) for OCA-DTPAGlu and OCA-DOTA, respectively) as confirmed by fluorescence spectroscopy. Fluorescence studies and circular dichroism experiments indicate, for the two compounds as well as for their gadolinium complexes (OCA-DOTA(Gd) and OCA-DTPAGlu(Gd)), the complete exposure of octreotide on the micelle surface, and the predominant presence of an antiparallel beta-sheet peptide conformation characterized by a beta-like turn. The high relaxivity value (r(1p) = 13.9 mM(-1) s(-1) at 20 MHz and 25 degrees C), measured for micelles obtained by the gadolinium complex OCA-DTPAGlu(Gd), indicates these aggregates as promising target-selective magnetic resonance imaging (MRI) contrast agents.