High proton relaxivity for gadolinium oxide nanoparticles

Objective: Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The objective of the present study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm) Gd₂O₃ nanocrystals. Materials and methods: Gd₂O₃ nanocrystals were synthesized by a colloidal method and capped with diethylene glycol (DEG). The oxidation state of Gd₂O₃ was confirmed by X-ray photoelectron spectroscopy. Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements were performed in aqueous solutions and cell culture medium (RPMI). Results: Results showed a considerable relaxivity increase for the Gd₂O₃–DEG particles compared to Gd-DTPA. Both T ₁ and T ₂ relaxivities in the presence of Gd₂O₃–DEG particles were approximately twice the corresponding values for Gd–DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low concentrations was predicted for the nanoparticle solutions, using experimental data to simulate a T₁-weighted spin echo sequence. Conclusion: The study indicates the possibility of obtaining at least doubled relaxivity compared to Gd–DTPA using Gd₂O₃–DEG nanocrystals as contrast agent. The high T ₁ relaxation rate at low concentrations of Gd₂O₃ nanoparticles is very promising for future studies of contrast agents based on gadolinium-containing nanocrystals.     

Synthesis, Characterization of α-Oxopentanedioic Acid-Isonicotinoyl Hydrazone Rare Earth-Complexes and Relaxivity of Gd-complex

Themagneticresonanceimaging (MRI)tech niqueforthemedicineisveryusefultodiagnosepre tumorandbloodvesseldiseaseinheartandbrainandothermalignantpre diseases .Therefore ,specialatten tionhasbeenalsopaidtoMRIcontrastagents ,whichareindispensablediagnosingdrugsforthemagneticresonanceimagingtechnique[1,2 ] .Gadolinium (Ⅲ)complexwithsomepolycarboxylicandpolyaminelig ands ,suchasGd(DTPA)·nH2 O ,waswidelyusedincliniclongago .OurpreviousworkshowsthatsomepolycarboxylicSchiffbasecomplexeswithrareea…     

Size-regulated group separation of CoFe2O4 nanoparticles using centrifuge and their magnetic resonance contrast properties

Magnetic nanoparticle (MNP)-based magnetic resonance imaging (MRI) contrast agents (CAs) have been the subject of extensive research over recent decades. The particle size of MNPs varies widely and is known to influence their physicochemical and pharmacokinetic properties. There are two commonly used methods for synthesizing MNPs, organometallic and aqueous solution coprecipitation. The former has the advantage of being able to control the particle size more effectively; however, the resulting particles require a hydrophilic coating in order to be rendered water soluble. The MNPs produced using the latter method are intrinsically water soluble, but they have a relatively wide particle size distribution. Size-controlled water-soluble MNPs have great potential as MRI CAs and in cell sorting and labeling applications. In the present study, we synthesized CoFe₂O₄ MNPs using an aqueous solution coprecipitation method. The MNPs were subsequently separated into four groups depending on size, by the use of centrifugation at different speeds. The crystal shapes and size distributions of the particles in the four groups were measured and confirmed by transmission electron microscopy and dynamic light scattering. Using X-ray diffraction analysis, the MNPs were found to have an inverse spinel structure. Four MNP groups with well-selected semi-Gaussian-like diameter distributions were obtained, with measured T₂ relaxivities (r₂) at 4.7 T and room temperature in the range of 60 to 300 mM⁻¹s⁻¹, depending on the particle size. This size regulation method has great promise for applications that require homogeneous-sized MNPs made by an aqueous solution coprecipitation method. Any group of the CoFe₂O₄ MNPs could be used as initial base cores of MRI T₂ CAs, with almost unique T₂ relaxivity owing to size regulation. The methodology reported here opens up many possibilities for biosensing applications and disease diagnosis.

PACS

75.75.Fk, 78.67.Bf, 61.46.Df     

Synthesis route and three different core-shell impacts on magnetic characterization of gadolinium oxide-based nanoparticles as new contrast agents for molecular magnetic resonance imaging

Despite its good resolution, magnetic resonance imaging intrinsically has low sensitivity. Recently, contrast agent nanoparticles have been used as sensitivity and contrast enhancer. The aim of this study was to investigate a new controlled synthesis method for gadolinium oxide-based nanoparticle preparation. For this purpose, diethyleneglycol coating of gadolinium oxide (Gd₂O₃-DEG) was performed using new supervised polyol route, and small particulate gadolinium oxide (SPGO) PEGylation was obtained with methoxy-polyethylene-glycol-silane (550 and 2,000 Da) coatings as SPGO-mPEG-silane550 and 2,000, respectively. Physicochemical characterization and magnetic properties of these three contrast agents in comparison with conventional Gd-DTPA were verified by dynamic light scattering transmission electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray diffraction, vibrating sample magnetometer, and the signal intensity and relaxivity measurements were performed using 1.5-T MRI scanner.As a result, the nanoparticle sizes of Gd₂O₃-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000 could be reached to 5.9, 51.3, 194.2 nm, respectively. The image signal intensity and longitudinal (r₁) and transverse relaxivity (r₂) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r₂/r₁ ratios of 1.13, 0.89, 33.34, and 33.72 for Gd-DTPA, Gd₂O₃-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000, respectively.The achievement of new synthesis route of Gd₂O₃-DEG resulted in lower r₂/r₁ ratio for Gd₂O₃-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r₂/r₁ ratios of two PEGylated-SPGO contrast agents in our study in comparison with r₂/r₁ ratio of previous PEGylation (r₂/r₁ = 81.9 for mPEG-silane 6,000 MW) showed that these new three introduced contrast agents could potentially be proper contrast enhancers for cellular and molecular MR imaging.     

On Water and its Effect on the Performance of T1-Shortening Contrast Agents

The performance of low molecular weight Gd³⁺ chelates as T₁-shortening contrast agents for MRI is limited by their rapid rate of molecular tumbling, which makes them very sensitive to factors that alter the rate of molecular reorientation. Unlike the interactions of these chelates with other solutes present in solution, which have been widely studied, the effect of the solvent water itself on tumbling seems to have been largely ignored. Water has long been known to adopt structures that vary from freely diffusing molecules on one extreme and a more “ice-like” structure on the other. A variety of salts can be used to alter this “structure” of water. Relaxometric studies on inner and outersphere Gd³⁺ chelates were performed in the presence of both structure making and structure breaking salts. The addition of structure-making salts to low molecular weight Gd³⁺ chelates was found to increase both the second- and outer-sphere contributions to relaxivity. These results point to a slowing of molecular tumbling arising from an increase solvent structure and therefore microviscosity. The implication of these findings is that the performance of low molecular weight Gd³⁺ contrast agents is not, as generally assumed, constant in the absence of secondary interactions but may vary depending upon the nature of the solution in which it is dissolved.     

Determination of in vivo rat muscle Gd-DTPA relaxivity at 6.3 T

For the in vivo relaxivity of Gd-DTPA at 6.3 T in rat muscle a value of 2.7±0.5 (mM s)⁻¹ was found, and for the in vitro value in water 3.00±0.56 (mM s)⁻¹ at 37°C. The temperature dependence of the in vitro relaxivity was −0.087 (mM s °C)⁻¹. The relation between1/T ₁ and the tissue Gd-DTPA concentration is linear for the normally used in vivo Gd-DTPA concentration range     

P792: a rapid clearance blood pool agent for magnetic resonance imaging: preliminary results

An original MRI contrast agent, called P792, is described. P792 is a gadolinium macrocyclic compound based on a Gd-DOTA structure substituted by hydrophilic arms. The chemical structure of P792 has been optimized in order to provide (1) a high r₁ relaxivity in the clinical field for MRI: 29 mM⁻¹ x s⁻¹ at 60 MHz. (2) a high biocompatibility profile and (3) a high molecular volume: the apparent hydrodynamic volume of P792 is 125 times greater than that of Gd-DOTA. As a result of this high molecular volume, P792 presents an unusual pharmacokinetic profile, as it is a Rapid Clearance Blood Pool Agent (RCBPA) characterized by limited diffusion across the normal endothelium. The original pharmacokinetic properties of this RCBPA are expected to be well suited to MR coronary angiography, angiography, perfusion imaging (stress and rest), and permeability imaging (detection of ischemia and tumor grading). Further experimental imaging studies are ongoing to define the clinical value of this compound.