Physicochemical Properties of Mixed Micellar Aggregates Containing CCK Peptides and Gd Complexes Designed as Tumor Specific Contrast Agents in MRI(462 views) Accardo A, Tesauro D, Roscigno P, Gianolio E, Paduano L, D'Errico G, Pedone C, Morelli G
J Am Chem Soc (ISSN: 0002-7863, 0002-2786, 1520-5126), 2004 Mar 17; 126(10): 3097-3107.
CIRPeB, Department of Biological Chemistry, University of Naples Federico II, Via Mezzocannone, 6, Naples, 1-80134, Italy
Department of Chemistry, University of Naples Federico II, Via Cynthia, Naples, 1-80126, Italy
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Physicochemical Properties of Mixed Micellar Aggregates Containing CCK Peptides and Gd Complexes Designed as Tumor Specific Contrast Agents in MRI
New amphiphilic molecules containing a bioactive peptide or a claw moiety have been prepared in order to obtain mixed micelles as target-specific contrast agents in magnetic resonance imaging. The first molecule, C 18H37CONH(AdOO)2-G-CCK8 (C18CCK8), contains a C18 hydrophobic moiety bound to the C-terminal cholecystokinin octapeptide amide (CCK 26-33 or CCK8). The second amphiphilic compound, C18H 37CONHLys(DTPAGlu)CONH2 (C18DTPAGlu) or its gadolinium complex, (C18DTPAGlu(Gd)), contains the same C18 hydrophobic moiety bound, through a lysine residue, to the DTPAGlu chelating agent. The mixed aggregates as well as the pure C18DTPAGlu aggregate, in the presence and absence of Gd, have been fully characterized by surface tension measurements, FT-PGSE-NMR, fluorescence quenching, and small-angle neutron scattering measurements. The structural characterization of the mixed aggregates C18DTPAGlu(Gd)-C18CCK8 indicates a spherical arrangement of the micelles with an external shell of ∼21 Å and an inner core of ∼20 Å. Both the DTPAGlu(Gd) complexes and the CCK8 peptides point toward the external surface. The measured values for relaxivity in saline medium at 20 MHz proton Larmor frequency and 25 °C are 18.7 mM-1 s-1. These values show a large enhancement in comparison with the isolated DTPAGlu(Gd) complex.
Physicochemical Properties of Mixed Micellar Aggregates Containing CCK Peptides and Gd Complexes Designed as Tumor Specific Contrast Agents in MRI
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