Diagnostic imaging using rare-earth chelates

A new class of polyazamacrocyclic chelates of terbium is studied that have rich spectroscopic properties, tissue selectivity [1], millisecond fluorescence lifetimes, sharply spiked emission spectra (<15 nm FWHM), large Stokes shifts (>280 nm), good water solubility [1] and high fluorescence quantum yields (0.6 for PCTMB) [1]. We report our in vitro and ex vivo spectroscopic evaluation of these chelates. Additionally, results from cellular binding specificity studies using Sprague-Dawley rats with UMR 108 osteosarcomas are presented. Finally, endoscopic imaging of dosed tissue demonstrates the potential to use the Tb(III) chelates as contrast enhancement markers.     

镧系铕配位羧甲基壳聚糖止血海绵的研究

本研究以羧甲基壳聚糖与镧系金属铕水合物进行配位,经发泡和冷冻干燥工艺制备得到镧系铕配位羧甲基壳聚糖止血海绵。通过扫描电镜(SEM)分析、吸液倍率测试、荧光光谱分析、大鼠背部止血实验和抑菌试验分别对该止血海绵的物理、化学及生物性能进行研究。该止血海绵呈多孔层状,吸液率达30~33倍,具有红色特征荧光性能。用于大鼠背部出血时,能迅速止血,粘附创面。对大肠杆菌、金黄色葡萄球菌、枯草杆菌有抑菌作用。该止血海绵可用于创面止血抑菌、特殊标记感染区和特征光学显示,在外科手术和家庭护理等方面具有很好的前景。     

Growth of lanthanide-doped LiGdF4 nanoparticles induced by LiLuF4 core as tri-modal imaging bioprobes

Multimodal imaging can compensate for the deficiencies and incorporate the advantages of individual imaging modalities. In this paper, we demonstrated the synthesis of core–shell nanocomposites LiLuF₄@LiGdF₄:Yb,Er/Tm constituted of tetragonal LiLuF₄ nanoparticles as core and Yb,Er/Tm-codoped LiGdF₄ as shell. LiLuF₄@LiGdF₄:Yb,Er/Tm nanoparticles display brighter upconversion luminescence (UCL) than NaGdF₄:Yb,Er/Tm nanoparticles with the same size under continuous-wave excitation at 980 nm. The active shell layer of LiGdF₄:Yb,Er/Tm not only provide the UCL center, but also serve as magnetic resonance (MR) imaging contrast agent. To further improve the UCL intensity, the inert LiGdF₄ shell was coated on the LiLuF₄@LiGdF₄:Yb,Er/Tm nanoparticles. Furthermore, LiLuF₄@LiGdF₄:Yb,Tm@LiGdF₄ nanoparticles have been successfully applied to UCL/X-ray computed tomography (CT)/MR tri-modal imaging on the modal of tumor-bearing mice.     

Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery

We have synthesized a biomaterial consisting of Gd(III) ions chelated to lipid-coated, size-selected microbubbles for utility in both magnetic resonance and ultrasound imaging. The macrocyclic ligand DOTA-NHS was bound to PE headgroups on the lipid shell of pre-synthesized microbubbles. Gd(III) was then chelated to DOTA on the microbubble shell. The reaction temperature was optimized to increase the rate of Gd(III) chelation while maintaining microbubble stability. ICP-OES analysis of the microbubbles determined a surface density of 7.5 × 10⁵ ± 3.0 × 10⁵ Gd(III)/μm² after chelation at 50 °C. The Gd(III)-bound microbubbles were found to be echogenic in vivo during high-frequency ultrasound imaging of the mouse kidney. The Gd(III)-bound microbubbles also were characterized by magnetic resonance imaging (MRI) at 9.4 T by a spin-echo technique and, surprisingly, both the longitudinal and transverse proton relaxation rates were found to be roughly equal to that of no-Gd(III) control microbubbles and saline. However, the relaxation rates increased significantly, and in a dose-dependent manner, after sonication was used to fragment the Gd(III)-bound microbubbles into non-gas-containing lipid bilayer remnants. The longitudinal (r₁) and transverse (r₂) molar relaxivities were 4.0 ± 0.4 and 120 ± 18 mM⁻¹s⁻¹, respectively, based on Gd(III) content. The Gd(III)-bound microbubbles may find application in the measurement of cavitation events during MRI-guided focused ultrasound therapy and to track the biodistribution of shell remnants.     

Determination of enantiomeric composition of ibuprofen in bulk drug by proton nuclear magnetic resonance spectroscopy with a chiral lanthanide chelate

The enantiomeric composition of ibuprofen was determined in a simple and reliable manner by proton nuclear magnetic resonance spectroscopy with a chiral lanthanide chelate. Optimum complexation with the europium (III) chelate took place in CCl₄ after conversion of the enantiomeric sample into a mixture of methyl esters. The optimization of the experimental conditions in terms of substrate concentration and lanthanide chelate to substrate molar ratio led to two sets of signals of utility for quantitative purposes. Analysis of synthetic enantiomeric mixtures by the proposed method demonstrated excellent agreement between the assay results and the known masses of each enantiomer present in the mixture samples. The average ± S.D. recovery values were 99.39 ± 0.92 and 99.42 ± 0.68% (n = 10) of (S)-(+)-ibuprofen depending on whether the quantitation was based on the -methyl protons or ester methyl protons, respectively.