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.
Morisco
Anna
A
Department of Biological Sciences, CIRPeB, University of Naples "Federico II" and IBB CNR, Via Mezzocannone 16, 80134 Naples, Italy.
Accardo
Antonella
A
Gianolio
Eliana
E
Tesauro
Diego
D
Benedetti
Ettore
E
Morelli
Giancarlo
G
D003287:Contrast Media / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008823:Micelles; D015394:Molecular Structure; D015282:Octreotide / Q000737:chemistry*
D003287:Contrast Media; D008823:Micelles; D015282:Octreotide