What are exposure biomarkers of rare earth elements for the ionic rare earth occupational population?

Rare earth elements (REEs) are widely utilized in industries. However, The specific exposure features of REEs and potential biomarkers of exposure in occupational populations remain unclear. In this study, we evaluated the external and internal REEs exposure levels among the participants working in the ionic rare earth smelting plant. For the external exposure, the concentrations of 14 REEs and total rare earth elements (ΣREEs) in airborne particles were significantly elevated in the REEs-exposed versus non-exposed group (P < 0.05). Meanwhile, the levels of Yttrium (Y), Gadolinium (Gd), Terbium (Tb), Dysprosium (Dy), Holmium (Ho), Thulium (Tm), Ytterbium (Yb), and ΣREEs in urine were higher in the REEs-exposed group compared to the non-exposed group (P < 0.05). Notably, a significant positive correlation was observed between Y in both the airborne particles and urine samples as well as Gd, and the Spearman correlation coefficient was 0.53 and 0.39 respectively, both P < 0.05. Conversely, no statistically significant differences were found in the levels of 15 REEs or ΣREEs in the blood samples between the REEs-exposed group and non-exposed group. Moreover, the concentrations of ΣREEs and 9 REEs in nail samples of the exposed group were significantly higher than those of the non-exposed group (P < 0.05), and the composition ratios of REEs in the nail samples closely resembled those found in individual airborne particles. Therefore, nail and urine samples were proposed to reflect long-term and short-term exposure to ionic rare earth respectively. Exposure biomarkers confirmed by external and internal exposure characteristics accurately provide the situation of human exposure to REEs environment, and have profound significance for monitoring and evaluating the level of REEs pollution in human body. It also provides a vital basis to find out the effect biomarkers, susceptible biomarkers and the health effects of rare earth environment for the future research.

Synthesis and characterization of high-sensitivity Dy,Eu co-doped CaSO4 thermoluminescent phosphor using coprecipitation technique.

In this work, (99 - x)CaSO4 -Dy2 O3 -xEu2 O3 , (where x = 0, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5) thermoluminescence phosphors were prepared using a coprecipitation method. The thermoluminescence (TL) dosimetry (TLD) characteristics such as TL sensitivity, dose-response, minimum detectable dose, thermal fading, and the effect of sunlight on the prepared phosphors were investigated. The obtained results indicated that the most sensitive phosphor was obtained at x = 0.05. Large thermal fading of 6% after 1 h and 26% after 24 h from irradiation followed by 71% after 1 month with no additional fading was observed within a time frame exceeding 2 months throughout the remaining duration of the investigation, which also spanned over 2 months. Despite the phosphor's high fading rate, the relative sensitivity of the prepared samples was ~90% compared with TLD-100. The marked effect of day sunlight was also determined. High dose-response within the low-dose range from 0.01 to 5 Gy was observed. The obtained results suggested that the synthesized phosphor is well suited for applications involving radiation biology and radiotherapy dosimetry.

Nickel sulfide and dysprosium-doped nickel sulfide nanoparticles: Dysprosium-induced variation in properties, in vitro chemo-photothermal behavior, and antibacterial activity.

Newer materials for utilization in multi-directional therapeutic actions are investigated, considering delicate design principles involving size and shape control, surface modification, and controllable drug loading and release. Multi-faceted properties are imparted to the engineered nanoparticles, like magnetism, near-infrared absorption, photothermal efficiency, and suitable size and shape. This report presents nickel sulfide and dysprosium-doped nickel sulfide nanoparticles with poly-ß-cyclodextrin polymer coating. The nanoparticles belong to the orthorhombic crystal systems, as indicated by X-ray diffraction studies. The size and shape of the nanoparticles are investigated using Transmission Electron Microscope (TEM) and a particle-size analyzer. The particles show soft ferromagnetic characteristics with definite and moderate saturation magnetization values. The nickel sulfide nanoparticles' in vitro anticancer and antibacterial activities are investigated in free and 5-fluorouracil/penicillin benzathine-loaded forms. The 5-fluorouracil-encapsulation efficiency of the nanoparticles is around 87%, whereas it is above 92% in the case of penicillin benzathine. Both drugs are released slowly in a controlled fashion. The dysprosium-doped nickel sulfide nanoparticles show better anticancer activity, and the efficacy is more significant than the free drug. The nanoparticles are irradiated with a low-power 808 nm laser. The dysprosium-doped nickel sulfide nanoparticles attain a higher temperature on irradiation, i.e., above 59 °C. The photothermal conversion efficiency of this material is determined, and the significance of dysprosium doping is discussed. Contrarily, the undoped nickel sulfide nanoparticles show more significant antibacterial activity. This study presents a novel designed nanoparticle system and the exciting variation of properties on dysprosium doping in nickel sulfide nanoparticles.

Predicting acute severe toxicity for head and neck squamous cell carcinomas by combining dosimetry with a radiosensitivity biomarker: a pilot study.

OBJECTIVE: Radiotherapy (RT) against head and neck squamous cell carcinomas (HNSCC) may lead to severe toxicity in 30-40% of patients. The normal tissue complication probability (NTCP) models, based on dosimetric data refined the normal tissue dose/volume tolerance guidelines. In parallel, the radiation-induced nucleoshuttling (RIANS) of the Ataxia-Telangiectasia Mutated protein (pATM) is a predictive approach of individual intrinsic radiosensitivity. Here, we combined NTCP with RADIODTECT©, a blood assay derived from the RIANS model, to predict RT toxicity in HNSCC patients. METHODS: RADIODTECT© cutoff values (i.e. 57.8 ng/mL for grade⩾2 toxicity and 46 ng/mL for grade⩾3 toxicity) have been previously assessed. Validation was performed on a prospective cohort of 36 HNSCC patients treated with postoperative RT. Toxicity was graded with the Common Terminology Criteria for Adverse Events (CTCAE) scale and two criteria were considered: grade⩾2 oral mucositis (OM2), grade⩾3 mucositis (OM3) and grade⩾2 dysphagia (DY2), grade⩾3 dysphagia (DY3). pATM quantification was assessed in lymphocytes of HNSCC patients. The discrimination power of the pATM assay was evaluated through the Area Under the Receiver Operator Characteristics Curve (AUC-ROC). Two previously described NTCP models were considered, including the dose to the oral cavity and the mean dose to the parotid glands (OM2 and OM3) and the dose to the oral cavity, to the larynx and the volume of pharyngeal constrictor muscles (DY2 and DY3). RESULTS: Combining NTCP models with RADIODTECT© blood test improved the AUC-ROC. Considering the prediction of mucositis, AUC-ROCNTCP+RADIODTECT©=0.80 was for OM2, and AUC-ROCNTCP+RADIODTECT©=0.78 for OM3. Considering the prediction of acute dysphagia, AUC-ROCNTCP+RADIODTECT©=0.71 for DY2 and for DY3. CONCLUSIONS: Combining NTCP models with a radiosensitivity biomarker might significantly improve the prediction of toxicities for HNSCC patients.

High precision half-life measurement of the extinct radio-lanthanide Dysprosium-154.

Sixty years after the discovery of 154Dy, the half-life of this pure alpha-emitter was re-measured. 154Dy was radiochemically separated from proton-irradiated tantalum samples. Sector field- and multicollector-inductively coupled plasma mass spectrometry were used to determine the amount of 154Dy retrieved. The disintegration rate of the radio-lanthanide was measured by means of α-spectrometry. The half-life value was determined as (1.40 ± 0.08)∙106 y, with an uncertainty reduced by a factor of ~ 10 compared to the currently adopted value of (3.0 ± 1.5)∙106 y. This precise half-life value is useful for the the correct testing and evaluation of p-process nucleosynthetic models using 154Dy as a seed nucleus or as a reaction product, as well as for the safe disposal of irradiated target material from accelerator driven facilities. As a first application of the half-life value determined in this work, the excitation functions for the production of 154Dy in proton-irradiated Ta, Pb, and W targets were re-evaluated, which are now in agreement with theoretical calculations.

Non-cytotoxic Dy3+ activated La10W22O81 nanophosphors for UV based cool white LEDs and anticancer applications.

White-light-emitting La10W22O81 (LWO): xDy3+ (0.5 ≤ x ≤ 10 mol%) nanocrystalline phosphors were developed by a facile hydrothermal assisted solid-state reaction. X-ray diffraction (XRD) pattern indicated that the prepared samples adopted orthorhombic crystal structures. The agglomeration of uniform nanorods was identified from the FE-SEM analysis of the optimized LWO: 1.5 mol% Dy3+ nanocrystalline phosphors. Additionally, transmission electron microscope, scanning transmission electron microscopy, selected area electron diffraction, and X-ray photoelectron spectroscopy were employed to explore the surface morphology, size, interplanar distance, and chemical composition with valence states of the LWO: 1.5 mol% Dy3+ phosphors, respectively. By exciting with 387 nm, the LWO: Dy3+ emission spectra showed two intense peaks at 476 nm (4F9/2→6H15/2) and 571 nm (4F9/2→6H13/2) and a shoulder peak at 659 nm (4F9/2→6H11/2). Optimum emission intensity was achieved for 1.5 mol% Dy3+ in the LWO host lattice. The luminescence quenching beyond 1.5 mol% Dy3+ is attributed to the dipole-dipole interactions when the Dy3+ (donor) and Dy3+ (acceptor) ions are at a critical distance of 58.53 Å. Photometric studies were conducted to evaluate the performance and practical applicability of the phosphors. The CIE chromaticity diagram suggests that the LWO: 1.5 mol% Dy3+ nanophosphor conspicuously exhibits cool white light. Therefore, this material could be a promising and potential white light-emitting nanocrystalline phosphor material for white light emitting diodes (LEDs) under near-UV excitation. In addition, the toxicity of the optimized nanophosphor in normal WI-38 lung fibroblast cells and MCF-7 breast cancer cells was examined. Surprisingly, LWO: 1.5 mol% Dy3+ nanophosphor was found to be non-cytotoxic to normal cells, but extremely toxic to cancer cells. Therefore, the nanophosphor materials can be considered potential candidates for biomedical applications, particularly for cancer treatment.

Heterogeneous Iron Oxide/Dysprosium Oxide Nanoparticles Target Liver for Precise Magnetic Resonance Imaging of Liver Fibrosis.

Challenges remain in precisely diagnosing the progress of liver fibrosis in a noninvasive way. We here synthesized small (4 nm) heterogeneous iron oxide/dysprosium oxide nanoparticles (IO-DyO NPs) as a contrast agent (CA) for magnetic resonance imaging (MRI) to precisely diagnose liver fibrosis in vivo at both 7.0 and 9.4 T field strength. Our IO-DyO NPs can target the liver and show an increased T2 relaxivity along with an increase of magnetic field strength. At a ultrahigh magnetic field, IO-DyO NPs can significantly improve spatial/temporal image resolution and signal-to-noise ratio of the liver and precisely distinguish the early and moderate liver fibrosis stages. Our IO-DyO NP-based MRI diagnosis can exactly match biopsy (a gold standard for liver fibrosis diagnosis in the clinic) but avoid the invasiveness of biopsy. Moreover, our IO-DyO NPs show satisfactory biosafety in vitro and in vivo. This work illustrates an advanced T2 CA used in ultrahigh-field MRI (UHFMRI) for the precise diagnosis of liver fibrosis via a noninvasive means.

Impact of dysprosium doped (Dy) zinc ferrite (ZnFe2o4) nanocrystals in photo- fenton exclusion of recalcitrant organic pollutant.

The issue of effluent, especially organic colorants from several manufacturing units overlays an immense delinquent of the current epoch owing to its effect on oncogenic health hazards. Thus, Rare Earth Metal dysprosium (Dy) doped Zinc Ferrite (ZnFe2O4) were as-synthesized by a facile co-precipitation technique as an effectual nano photocatalyst intended to the amputation of these noxious dyes. The structural, functional, optical, magnetic, and degradation properties of this RE (Dy3+) doped ions were investigated using various characterizations, such as crystallite size (D) and several parameters (cation distribution, oxygen positional parameters, and bond length) were determined using XRD (X-ray diffraction) and it was found that as the dy3+ ion concentration increases the speck size decreased and the grain size remained within nano regime, which intern affects the surface area. From BET analysis it was found that on increasing the doping concentration, the surface area increases which pave a substantial role in the photo-Fenton activity. By using FT-IR (Fourier-transform infrared spectroscopy) various functional parameters (elastic, interionic bonds, ion distribution, etc.) were determined. Raman spectra had no extra peak formation which is seen to have pure phase formation of the as-synthesized samples. HR-TEM (High-Resolution Transmission Electron Microscopy analysis were done to determine the nature of the sample, the as-synthesized magnetic samples exhibit a polycrystalline formation with cubical agglomeration. The magnetic property was very significant for x = 0.10 concentration. As-synthesized (Fe0.9064Zn0.0936) [Fe1.0936Dy0.1Zn0.8064] O4) exhibits a momentous photo - Fenton activity against MB (Methylene blue), its removal efficiency was found to be 97.3% after 45 min. Also, this spinel ferrite acts as a magnetic recyclable catalyst even after 5 cycles with an insignificant lessening of elements and photo-Fenton activity.

Dysprosium and Holmium Vanadate Nanoprobes as High-Performance Contrast Agents for High-Field Magnetic Resonance and Computed Tomography Imaging.

We describe a wet chemical method for the synthesis of uniform and well-dispersed dysprosium vanadate (DyVO4) and holmium vanadate (HoVO4) nanoparticles with an almost spherical shape and a mean size of ∼60 nm and their functionalization with poly(acrylic acid). The transverse magnetic relaxivity of both systems at 9.4 T is analyzed on the basis of magnetic susceptibility and magnetization measurements in order to evaluate their potential for application as high-field MRI contrast agents. In addition, the X-ray attenuation properties of these systems are also studied to determine their capabilities as computed tomography contrast agent. Finally, the colloidal stability under physiological pH conditions and the cytotoxicity of the functionalized NPs are also addressed to assess their suitability for bioimaging applications.

Highly brain-permeable apoferritin nanocage with high dysprosium loading capacity as a new T2 contrast agent for ultra-high field magnetic resonance imaging.

High sensitivity at ultra-high field (UHF) and sufficient potential to penetrate the brain are the most desirable characteristics in the development of contrast agents (CAs) for magnetic resonance imaging (MRI). However, incorporating such qualities into a single nanocarrier is challenging. Herein, we report a new strategy for a highly brain-permeable MR CA with high sensitivity at UHF by loading dysprosium chelates (DyL) in apoferritin cavities (Apo-DyL). We also design the chelate ligand structure to increase DyL loading capacity within the apoferritin cavity. Using the intracerebroventricular (ICV) injection approach as a new delivery route for Apo-DyL, we demonstrate that apoferritin loaded with DyL can penetrate the brain-ventricular barrier and diffuse into the brain. This brain-permeable capability is unique to Apo-DyL, compared with other types of nanoparticles used in MRI. Apo-DyL also shows significant increase in MR sensitivity of DyL at UHF. Furthermore, based on brain tumor imaging at UHF, Apo-DyL can significantly enhance the tumor for a lower dose of the CA than the previously reported Gd- or Mn-loaded apoferritin nanoplatform. Therefore, Apo-DyL can be a novel nanoplatform that is a highly sensitive and versatile MR CA for UHF brain imaging.

Direct Recovery of the Rare Earth Elements Using a Silk Displaying a Metal-Recognizing Peptide.

Rare earth elements (RE) are indispensable metallic resources in the production of advanced materials; hence, a cost- and energy-effective recovery process is required to meet the rapidly increasing RE demand. Here, we propose an artificial RE recovery approach that uses a functional silk displaying a RE-recognizing peptide. Using the piggyBac system, we constructed a transgenic silkworm in which one or two copies of the gene coding for the RE-recognizing peptide (Lamp1) was fused with that of the fibroin L (FibL) protein. The purified FibL-Lamp1 fusion protein from the transgenic silkworm was able to recognize dysprosium (Dy3+), a RE, under physiological conditions. This method can also be used with silk from which sericin has been removed. Furthermore, the Dy-recovery ability of this silk was significantly improved by crushing the silk. Our simple approach is expected to facilitate the direct recovery of RE from an actual mixed solution of metal ions, such as seawater and industrial wastewater, under mild conditions without additional energy input.

STUDY OF EFFECT OF CONSECUTIVE HEATING ON THERMOLUMINESCENCE GLOW CURVES OF MULTI-ELEMENT TL DOSEMETER IN HOT GAS-BASED READER SYSTEM.

The objective of this paper is to study the effect of consecutive heating of TL elements of a thermoluminescence dosemeter (TLD) card in hot N2 gas-based TLD badge reader. The effect is studied by theoretical simulations of clamped heating profiles of the discs and resulting TL glow curves. The simulated temperature profile accounts for heat transfer to disc from hot gas as well as radiative and convective heat exchanges between the disc and the surrounding. The glow curves are simulated using 10 component glow peak model for CaSO4:Dy using the simulated temperature profile. The shape of the simulated glow curves and trend in total TL signal of the three discs were observed to match closely with the experimental observations when elevated surrounding temperature was considered for simulation. It is concluded that the readout (heating) of adjacent TLD disc affects the surrounding temperature leading to the changes in temperature profile of the next disc.

Bifunctional Mononuclear Dysprosium Complexes: Single-Ion Magnet Behaviors and Antitumor Activities.

Two mononuclear dysprosium complexes (Et3NH)[Dy(BrMQ)4]·H2O·DMF(BrMQ-Dy) and (Et3NH)[Dy(ClMQ)4]·H2O·DMF (ClMQ-Dy) (H-BrMQ = 5,7-dibromo-2-methyl-8-quinolinol, H-ClMQ = 5,7-dichloro-2-methyl-8-quinolinol) were synthesized and characterized. The Dy(III) ions in complexes BrMQ-Dy and ClMQ-Dy have a pseudo-D4d local symmetry. Magnetic characterizations reveal that complex BrMQ-Dy is a single-ion magnet and complex ClMQ-Dy exhibits field-induced slow magnetic relaxation behaviors. The calculated effective barriers of BrMQ-Dy, BrMQ-Dya, ClMQ-Dy, and ClMQ-Dya are 47.8, 27.3, 96.0, and 65.5 cm-1, respectively (BrMQ-Dya and ClMQ-Dya represent the desolvated samples of BrMQ-Dy and ClMQ-Dy, respectively). Ab initio calculations confirmed that coordination symmetry of the Dy(III) ions, electron-withdrawing ligands, and the guest molecules is a key factor affecting the magnetic dynamics of the two complexes. The IC50 values of BrMQ-Dy and ClMQ-Dy against BEL-7404, HeLa, and Hep-G2 cancer cells were 1.01-22.06 µM. Interestingly, two Dy(III) complexes were less toxic to normal HL-7702 cells. BrMQ-Dy and ClMQ-Dy significantly induced cell arrest at G2 phase and down-regulated the G2 phase-related protein levels. Various experiments suggested that BrMQ-Dy and ClMQ-Dy also caused dysfunction of mitochondrial pathways in HeLa cells. Taken together, the different in vitro anticancer activity of complexes BrMQ-Dy and ClMQ-Dy in the order of 5,7-dichloro substitution > 5,7-dibromo substitution.

Fast magnetic resonance fingerprinting for dynamic contrast-enhanced studies in mice.

PURPOSE: The goal of this study was to develop a fast MR fingerprinting (MRF) method for simultaneous T1 and T2 mapping in DCE-MRI studies in mice. METHODS: The MRF sequences based on balanced SSFP and fast imaging with steady-state precession were implemented and evaluated on a 7T preclinical scanner. The readout used a zeroth-moment-compensated variable-density spiral trajectory that fully sampled the entire k-space and the inner 10 × 10 k-space with 48 and 4 interleaves, respectively. In vitro and in vivo studies of mouse brain were performed to evaluate the accuracy of MRF measurements with both fully sampled and undersampled data. The application of MRF to dynamic T1 and T2 mapping in DCE-MRI studies were demonstrated in a mouse model of heterotopic glioblastoma using gadolinium-based and dysprosium-based contrast agents. RESULTS: The T1 and T2 measurements in phantom showed strong agreement between the MRF and the conventional methods. The MRF with spiral encoding allowed up to 8-fold undersampling without loss of measurement accuracy. This enabled simultaneous T1 and T2 mapping with 2-minute temporal resolution in DCE-MRI studies. CONCLUSION: Magnetic resonance fingerprinting provides the opportunity for dynamic quantification of contrast agent distribution in preclinical tumor models on high-field MRI scanners.

Structural, Mechanical, Imaging and in Vitro Evaluation of the Combined Effect of Gd3+ and Dy3+ in the ZrO2-SiO2 Binary System.

Mechanical strength and biocompatibility are considered the main prerequisites for materials in total hip replacement or joint prosthesis. Noninvasive surgical procedures are necessary to monitor the performance of a medical device in vivo after implantation. To this aim, simultaneous Gd3+ and Dy3+ additions to the ZrO2-SiO2 binary system were investigated. The results demonstrate the effective role of Gd3+ and Dy3+ to maintain the structural and mechanical stability of cubic zirconia ( c-ZrO2) up to 1400 °C, through their occupancy of ZrO2 lattice sites. A gradual tetragonal to cubic zirconia ( t-ZrO2 → c-ZrO2) phase transition is also observed that is dependent on the Gd3+ and Dy3+ content in the ZrO2-SiO2. The crystallization of either ZrSiO4 or SiO2 at elevated temperatures is delayed by the enhanced thermal energy consumed by the excess inclusion of Gd3+ and Dy3+ at c-ZrO2 lattice. The addition of Gd3+ and Dy3+ leads to an increase in the density, elastic modulus, hardness, and toughness above that of unmodified ZrO2-SiO2. The multimodal imaging contrast enhancement of the Gd3+ and Dy3+ combinations were revealed through magnetic resonance imaging and computed tomography contrast imaging tests. Biocompatibility of the Gd3+ and Dy3+ dual-doped ZrO2-SiO2 systems was verified through in vitro biological studies.

Light sheet microscopy and SrAl2 O4 nanoparticles codoped with Eu2+ /Dy3+ ions for cancer cell tagging.

Light sheet optical microscopy on strontium aluminate nanoparticles (SrAl2 O4 NPs)1 codoped with Eu2+ and Dy3+ was used for cancer cell tagging and tracking. The nanoparticles were synthesized by urea-assisted combustion with optimized percentage values of the 2 codoping rare-earth ions for cell viability and for lower cytotoxic effects. The optical properties of these materials showed an excitation wide range of wavelengths (λexc = 254-460 nm), a broad emission band (λem = 475-575 nm) with the maximum centered wavelength at 525 nm and a half lifetime within the seconds regime. The feasibility to measure the nanoparticle luminescence under the selective plane illumination configuration was studied by immersing the nanoparticles in 1% Agarose. The potential applicability of the synthesized nanophosphors for cancer cell tagging was demonstrated by using in vitro experiments with human breast adenocarcinoma MCF-7 cells. A single MCF-7 cell observed by the use of light sheet microscopy with UV excitation. The cell has been bio-labeled with FA-SrAl2 04 : Eu2+ , Dy3+ NPs and 4',6-diamidino-2-phenylindole, dihydrochloride for nucleus identification.

Dysprosium-Modified Tobacco Mosaic Virus Nanoparticles for Ultra-High-Field Magnetic Resonance and Near-Infrared Fluorescence Imaging of Prostate Cancer.

The increasing prevalence of ultra-high-field magnetic resonance imaging (UHFMRI) in biomedical research and clinical settings will improve the resolution and diagnostic accuracy of MRI scans. However, better contrast agents are needed to achieve a satisfactory signal-to-noise ratio. Here, we report the synthesis of a bimodal contrast agent prepared by loading the internal cavity of tobacco mosaic virus (TMV) nanoparticles with a dysprosium (Dy3+) complex and the near-infrared fluorescence (NIRF) dye Cy7.5. The external surface of TMV was conjugated with an Asp-Gly-Glu-Ala (DGEA) peptide via a polyethylene glycol linker to target integrin α2ß1. The resulting nanoparticle (Dy-Cy7.5-TMV-DGEA) was stable and achieved a high transverse relaxivity in ultra-high-strength magnetic fields (326 and 399 mM-1 s-1 at 7 and 9.4 T, respectively). The contrast agent was also biocompatible (low cytotoxicity) and targeted PC-3 prostate cancer cells and tumors in vitro and in vivo as confirmed by bimodal NIRF imaging and T2-mapping UHFMRI. Our results show that Dy-Cy7.5-TMV-DGEA is suitable for multiscale MRI scanning from the cellular level to the whole body, particularly in the context of UHFMRI applications.

A new paramagnetically shifted imaging probe for MRI.

PURPOSE: To develop and characterize a new paramagnetic contrast agent for molecular imaging by MRI. METHODS: A contrast agent was developed for direct MRI detection through the paramagnetically shifted proton magnetic resonances of two chemically equivalent tert-butyl reporter groups within a dysprosium(III) complex. The complex was characterized in phantoms and imaged in physiologically intact mice at 7 Tesla (T) using three-dimensional (3D) gradient echo and spectroscopic imaging (MRSI) sequences to measure spatial distribution and signal frequency. RESULTS: The reporter protons reside ∼6.5 Å from the paramagnetic center, resulting in fast T1 relaxation (T1 = 8 ms) and a large paramagnetic frequency shift exceeding 60 ppm. Fast relaxation allowed short scan repetition times with high excitation flip angle, resulting in high sensitivity. The large dipolar shift allowed direct frequency selective excitation and acquisition of the dysprosium(III) complex, independent of the tissue water signal. The biokinetics of the complex were followed in vivo with a temporal resolution of 62 s following a single, low-dose intravenous injection. The lower concentration limit for detection was ∼23 µM. Through MRSI, the temperature dependence of the paramagnetic shift (0.28 ppm.K-1 ) was exploited to examine tissue temperature variation. CONCLUSIONS: These data demonstrate a new MRI agent with the potential for physiological monitoring by MRI. Magn Reson Med 77:1307-1317, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Rare Earth Ion Mediated Fluorescence Accumulation on a Single Microbead: An Ultrasensitive Strategy for the Detection of Protein Kinase Activity at the Single-Cell Level.

A single microbead-based fluorescence imaging (SBFI) strategy that enables detection of protein kinase activity from single cell lysates is reported. We systematically investigated the ability of various rare earth (RE) ions, immobilized on the microbead, for specific capturing of kinase-induced phosphopeptides, and Dy(3+) was found to be the most prominent one. Through the efficient concentration of kinase-induced fluorescent phosphopeptides on a Dy(3+) -functionalized single microbead, kinase activity can be detected and quantified by reading the fluorescence on the microbead with a confocal fluorescence microscope. Owing to the extremely specific recognition of Dy(3+) towards phosphopeptides and the highly-concentrated fluorescence accumulation on only one microbead, ultrahigh sensitivity has been achieved for the SBFI strategy which allows direct kinase analysis at the single-cell level.

Single-Molecule-Magnet Behavior in a [2 × 2] Grid Dy(III)4 Cluster and a Dysprosium-Doped Y(III)4 Cluster.

Thanks to the MeCN hydrolysis in situ reaction, a [2 × 2] square grid Dy(III)4 cluster based on a polypyridyl triazolate ligand, [Dy4(OH)2(bpt)4(NO3)4(OAc)2] (1), was separated successfully and characterized through single-crystal X-ray diffraction and SQUID magnetometry. The frequency-dependent signals in the out-of-phase component of the susceptibility associated with slow relaxation of the magnetization confirmed that complex 1 displays single-molecule magnet (SMM) behavior. Two distinct slow magnetic relaxation processes, with effective energy barriers Ueff1 = 93 cm(-1) for fast relaxation and Ueff2 = 143 cm(-1) for slow relaxation observed under a zero direct-current field, are mainly attributed to the origin of single-ion behavior, which can be further acknowledged by the magnetic investigation of a dysprosium-doped yttrium cluster. Besides, it should be noted that complex 1 represents so far the highest energy barrier among the pure Dy(III)4 SMMs.