Physicochemical properties of mixed micellar aggregates containing CCK peptides and Gd complexes designed as tumor specific contrast agents in MRI

被引:83
作者
Accardo, A
Tesauro, D
Roscigno, P
Gianolio, E
Paduano, L
D'Errico, G
Pedone, C
Morelli, G
机构
[1] Univ Naples Federico II, Ctr Interuniv Ric Peptidi Bioattivi CIRP&B, I-80126 Naples, Italy
[2] Univ Naples Federico II, Dept Biol Chem, I-80126 Naples, Italy
[3] Univ Naples Federico II, Dept Chem, I-80126 Naples, Italy
[4] Univ Turin, Dept Chem, IFN, I-10125 Turin, Italy
关键词
D O I
10.1021/ja039195b
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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, C18H37CONH(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, C(18)H(37)CONHLys(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 similar to21 Angstrom and an inner core of similar to20 Angstrom. Both the DTPAGiu(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 degreesC are 18.7 mM(-1) s(-1). These values show a large enhancement in comparison with the isolated DTPAGlu(Gd) complex.
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页码:3097 / 3107
页数:11
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