A Polypeptide-Based, Membrane-Penetrating, Target-Specific Contrast Agent for Magnetic Resonance Molecular Imaging.

Molecular imaging based on magnetic resonance imaging (MRI) requires a contrast agent with high relaxivity and specificity. Much effort has been devoted to this goal over the past decades. In this work, we continue this endeavor by synthesizing an MRI contrast agent that can penetrate the cellular membrane and bind with specific proteins. It was characterized with one- and two-dimensional NMR spectroscopy, NMR micro-imaging, and mass spectroscopy. The target specificity has been further confirmed by both molecular dynamics simulation and micro-imaging on a living biological system. It is one of the largest of peptide-based bioactivated MRI contrast agents, and its relaxivity enhancement factor is among the highest of MRI contrast agents hitherto published. We envision interesting applications and extension of this smart MRI contrast agent with bio-specificity and high contrast for molecular imaging.

Design, synthesis, and in vitro evaluation of a binary targeting MRI contrast agent for imaging tumor cells.

A binary targeting vector that consists of peptide sequences of Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) motifs has been designed and synthesized using solid-phase peptide synthesis procedure. The vector is then coupled with Gd-DOTA to work as a targeting contrast agent (CA1) for magnetic resonance imaging of human lung adenocarcinoma cells A549. Its longitudinal relaxivity is measured to be 7.55 mM(-1) s(-1) in aqueous solution at a magnetic field of 11.7 T, which is higher than that of Magnevist (4.25 mM(-1) s(-1)) in the same conditions. The cell experiment shows, at the same concentration, uptake quantity of CA1 by A549 is much more than Magnevist and also superior over CA2 (a single targeting contrast agent contains only RGD). The uptake can be blocked by the targetable peptide containing RGD or NGR without coupling Gd. To summarize, CA1 has very good ability to target A549 and higher relaxivity than that of Magnevist. So CA1 is promising MRI contrast agent for high-resolution MR molecular imaging of human lung adenocarcinoma A549 cells.

In vitro assessment of the dual-targeting behavior of a peptide-based magnetic resonance imaging contrast agent.

In this study, a peptide-based dual-targeting magnetic resonance imaging (MRI) contrast agent (S8) was designed and synthesized. Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) were combined in the targeting vector so as to allow binding, on the surface of tumor cells, to integrin αvß3 and aminopeptidase N (CD13), respectively. The longitudinal relaxivity (r1) value of S8 was 8.297 mM-1sec-1 at a magnetic field of 11.7 T, which is approximately double the r1 value (4.25 mM-1sec-1) of Magnevist, a commercially available contrast agent. MDA-MB-231 human breast cancer cells (which overexpress αvß3) and human prostate cancer cells PC-3 (which overexpress CD13) were used to investigate the tumor­targeting behavior of S8. The results from the present study indicate that the designed contrast agent, S8, targets both MDA-MB­231 and PC-3 cells.

Temperature-controlled synthesis and luminescent properties of two novel coordination polymers modeled by hexa-carboxylate ligand derived from cyclotriphosphazene.

Solvothermal reactions of hexakis(4-formylphenoxy)cyclotriphosphazene (H(6)L1) with Cd(NO(3))(2)·4H(2)O in H(2)O/DMF under different synthesis temperatures produced two new compounds, namely, {[Cd(3)(C(42)H(24)O(18)P(3)N(3)) (H(2)O)(7)]·xGuest}(n) (1), and {[Cd(2)(C(42)H(24)O(18)P(3)N(3)) (H(2)O)(2)]·xGuest}(n) (2). Compound 1 exhibits a novel 3D framework adopting 2,4,6-connected 3-nodal topology with the point (Schläfli) symbol {4(4)·6(2)}{4(5)·6(2)·8(8)}{4} constructed from the joint of neutral Cd(2) SBUs, mono-Cd ions and L1 ligands. Compound 2 reveals a 2D crystal structure exhibiting a 3,6-connected 2-nodal kgd topology with the point (Schläfli) symbol {4(3)}(2){4(6)·6(6)·8(3)} constructed from the connection of Cd centers and L1 ligands. In these two compounds, the ligands L1 are fully deprotonated, whose six extended carboxyl arms connect six different/same metallic nodes to form high dimensional frameworks. The variable reaction temperature must be responsible for the higher coordination number and versatile coordination modes of carboxylates in 1 compared to the ones in 2, resulting in the formation of a distinct crystal structure. In the solid state, both complexes are photoluminescent (LMCT) at room temperature.

Self-assembly, structures, and photophysical properties of 4,4'-bipyrazolate-linked metallo-macrocycles with dimetal clips.

By employing functional diimine ligands coordinated dipalladium(II,II) or diplatinum(II,II) clips as corners and the coplanar 4,4'-bipyrazolate dianion (L(2-)) ligand as linker, a series of bipyrazolate-bridged metallo-macrocycles, namely, [M8L4](NO3)8 (M = Pd(dmbpy), 1; Pd(bpy), 2; Pt(bpy), 3a; Pd(phen), 4; Pt(phen), 5; Pd(15-crown-5-phen), 6; Pd(18-crown-6-phen), 8; Pd(benzo-24-crown-8-phen), 10a; Pt(15-crown-5-phen), 7a, Pt(18-crown-6-phen), 9a; Pt(benzo-24-crown-8-phen), 11a) and [M6L3](NO3)6 (M = Pt(bpy), 3b; Pt(15-crown-5-phen), 7b; Pt(18-crown-6-phen), 9b; Pd(benzo-24-crown-8-phen), 10b; Pt(benzo-24-crown-8-phen), 11b), have been synthesized through a directed self-assembly approach that involves spontaneous deprotonation of the 1H-bipyrazolyl ligands in aqueous solution. All these compounds have a crown-shaped cavity that can serve as host to solvent molecules and anions. The structures are characterized by elemental analysis, (1)H and (13)C NMR, ESI-MS, and in the cases of 1a (the BF4(-) salt of 1), 2a (the BF4(-) salt of 2), and 3b by single-crystal X-ray diffraction analysis. Photophysical properties for complexes 1 and 2 are discussed.

[Synthesis, characterization and relaxivity of dimeric DTPA-gadonium (III) complexes with long chain alkyl esters of L-lysine].

To look for new MRI (magnetic resonance imaging) contrast agents with higher relaxivity as well as liver-selecsivity, four novel ester-amino ligands were synthesized by bis-acylation of octadecanyl, hexadecanyl, tetradecanyl and dedecanyl L-lysine with diethylenetriaminepentaacetic acid mono-anhydride (DTPA-MA), respectively. The corresponding dimeric Gd(III) complexes were gained by the reaction of these ligands with GdCl3 x 6H2O. All ligands and complexes were characterized by FTIR, 1H NMR and elemental analysis. The longitudinal relaxation time (T1) was measured, and relevant longitudinal relaxivity (R1) of these neatral binuclear Gd(III) complexes is: 6.48, 6.02, 5.76 and 5.68 L x mmol(-1) x s(-1), respectively, and all are higher than that of Gd-DTPA (4.98 L x mmol(-1) x s(-1)) (300 MHz).