François Botteman

Dy-DTPA derivatives as relaxation agents for very high field MRI: The beneficial effect of slow water exchange on the transverse relaxivities

Proton longitudinal and transverse relaxivities of Dy(DTPA)2− and Dy‐DTPA bisamide derivatives (Dy(DTPA‐BA): Dy‐DTPA bisamide, Dy(DTPA‐BEA): Dy‐DTPA bisethylamide, Dy(DTPA‐BnBA): Dy‐DTPA bis‐n‐butylamide, and Dy(DTPA‐BBMA): Dy‐DTPA bisbismethylamide) were analyzed between 0.47 T and 18.8 T. Curie longitudinal relaxation was clearly observed at magnetic fields larger than 2.4 T, but the longitudinal relaxivities are limited by the fast rotation of the complexes. Rotational correlation times were separately assessed by deuterium relaxometry of the diamagnetic deuterated lanthanum analogs. Transverse relaxivity, which depends on the square of the magnetic field and on the residence time of the coordinated water molecule (τM), was more than 7.5 times larger at 18.8 T and 310 K for Dy(DTPA‐BA) and Dy(DTPA‐BEA) as compared to Dy(DTPA)2−. This difference is mainly related to the slower water exchange of the bisamide complexes, as confirmed by the values of τM measured by oxygen‐17 relaxometry. Such Dy‐complexes, characterized by relatively long τM values (τ M 310 larger than 100 ns but smaller than 1 μs), thus appear to be useful as negative T2 (or transverse) contrast agents for high‐field imaging. This was demonstrated by the spin‐echo images of phantoms obtained at 4.7 T on samples containing Dy(DTPA)2− and Dy(DTPA‐BEA). Magn Reson Med 47:1121–1130, 2002.

Enhancement of Transfection Efficiency Through Rapid and Noncovalent Post-PEGylation of Poly(Dimethylaminoethyl Methacrylate)/DNA Complexes

AbstractPurpose. The aim of this work was to develop a new strategy to intro- duce poly(ethylene glycol) (PEG) into methacrylate-based polymer/DNA complexes in order to produce hemocompatible particles able to transfect cells in the presence of serum. Methods. Atom transfer radical polymerization was used to synthesize a well-defined poly(2-(dimethylamino)ethyl methacrylate) homopolymer (PDMAEMA) and a poly(2-(dimethylamino)ethyl methacrylate-b-poly(ethylene glycol) α-methyl ether, ω-methacrylate) palm-tree-like copolymer (P(DMAEMA-b-MAPEG)). The complexes obtained by self assembly of the pCMVβ plasmid and the polymers were used to transfect Cos-7 cells. Their physical properties—particle size and zeta potential—were characterized respectively by dynamic light scattering and electrophoretic mobility measurements. Ex vivo hemocompatibility was also determined. Results. The PDMAEMA/pCMVβ complexes transfected Cos-7 cells exclusively in the absence of serum. Although the P(DMAEMA-b-MAPEG) copolymer had no transfection activity per se, the addition of the latter to pre-formed PDMAEMA/DNA complexes significantly enhanced the activity and allowed transfection even in the presence of serum. The presence of palm-tree-like copolymers also improved the hemocompatibility properties of the complexes. No effect on platelet counts was observed for P(DMAEMA-b-MAPEG)/pCMVβ complexes, whereas a decrease of platelets was clearly observed when blood cells were incubated with PDMAEMA/pCMVβ complexes. Conclusions. Such a synergistic effect of noncovalent PEGylation of poly(amino methacrylate)/DNA complexes allows a new and versatile approach to tune up transfection efficiency.

Synthesis, Variable Temperature and Pressure 17O NMR Study of Bis(alkylamide) Derivatives of [(Gd-DTPA)(H2O)]2− − An Assessment of the Substitution Effect on Water Exchange Kinetics

Reference LCIB-ARTICLE-2002-003View record in Web of Science Record created on 2006-02-15, modified on 2017-05-12

Optimising the design of paramagnetic MRI contrast agents: influence of backbone substitution on the water exchange rate of Gd-DTPA derivatives

Among other factors influencing the residence time of the coordinated water (τM) of paramagnetic contrast agents, the steric hindrance around the gadolinium ion seems to play a beneficial role. Such a crowding can be achieved by substituting the Gd-DTPA backbone on the C4 position. Several Gd-DTPA complexes carrying diverse groups at this position have thus been synthesised and characterised: Gd(S)-C4-Me-DTPA, Gd(S)-C4-n-Bu-DTPA, Gd(S)-C4-iBu-DTPA, Gd(S)-C4-iPr-DTPA, and Gd-C4-diMe-DTPA. τM has been measured through the evolution of the water oxygen-17 transverse relaxation rate as a function of the temperature. The data show a reduction of τM of Gd(S)-C4-Me-DTPA, Gd(S)-C4-n-Bu-DTPA, Gd(S)-C4-iBu-DTPA, Gd(S)-C4-iPr-DTPA, and Gd-C4-diMe-DTPA (τM310=91,82, 108,98, and 57 ns respectively, as compared to Gd-DTPA (τM310=143 ns)). At 310 K, the nuclear magnetic dispersion relaxation profiles of water protons are very similar for the five complexes which present longitudinal relaxivities slightly higher than those of Gd-DTPA. Regarding zinc transmetallation, C4-monosubstituted derivatives are more stable than Gd-DTPA. These results confirm that a judicious substitution of the DTPA skeleton allows for an acceleration of the coordinated water exchange rate. This observation can be useful for the design of vectorised contrast agents for molecular imaging.

Dy-complexes as high field T2 contrast agents: influence of water exchange rates.

Dy complexes can act as suitable negative (T2) contrast agents for Magnetic Resonance Imaging (MRI). As clinical MRI moves toward higher fields, tuning of the exchange rate of coordinated water molecules will become necessary to optimize the r2 relaxivity. For Dy complexes, this will require lengthening of the water residence time, a strategy opposite that required to optimize the r1 relaxivity of Gd complexes. However, very slow water exchange can be deleterious. This is illustrated here by a Dy complex that is characterized by a very slow water exchange. This complex, Dy-DOTA-4AmCE, is compared with several Dy-DTPA derivatives known for their efficacy as T2 contrast agents at high magnetic fields.

Removal of copper-based catalyst in atom transfer radical polymerization using different extraction techniques

Abstract Several methods allowing the removal of copper-based ATRP active complexes from crude amino-functionalized polymethacrylate chains are compared. Among them, precipitation in basic medium is one of the most efficient techniques since it allows high recovery yields (above 90%) with a residual metal content as low as 5 ppm. Extraction methods such as liquid-liquid phase separation and dialysis but also selective adsorption on acidic macroporous ion exchange resin constitute other attractive alternatives. As far as water-insoluble polymers are concerned, catalyst adsorption on alumina remains the most universal method and provides acceptable recovery efficiency. However, we want to stress the key-importance of the experimental adsorption conditions and above all the relative content of alumina used for catalyst extraction.