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Colossal piezomagnetic response in magnetically pressed Zr⁺⁴ substituted cobalt ferrites.

ABSTRACT: A remarkable 111% increase in magnetostriction (?) and 435% increase in strain sensitivity (d?/dH) (compared to normally compacted (NC) unsubstituted CoFe₂O₄ (CFO)) of Zr⁺⁴ doped CFO sample, Co_1.2Zr_0.2Fe_1.6O₄, prepared by magnetic field assisted compaction, have been reported in this study. Magnetic field assisted compaction (MC) has been employed to process Zr-doped cobalt ferrites, Co_1+xZr_xFe_2-2xO₄ (0???×???0.4), to further improve the magnetoelastic properties. Saturation magnetization (M _S ) and coercivity (H _C ) increase from ~426?kA/m and ~4.4?kA/m respectively, for x?=?0, to ~552?kA/m and ~7.11?kA/m respectively for x?=?0.2. Dramatic increase in ? was observed for MC samples (~ -360?ppm and ~-380?ppm for x?=?0 and x?=?0.2 respectively) compared to the NC samples (~-181?ppm and ~-185?ppm for x?=?0 and x?=?0.2 respectively). A remarkable quadruple increase in d?/dH was observed in Zr-doped (x?=?0.2) cobalt-ferrite (~4.3?×?10^-9 A^-1m) compared to that of unsubstituted cobalt-ferrite (~1.24?×?10^-9 A^-1m), while a fivefold increase in d?/dH was observed for magnetically compacted (MC) Zr doped cobalt ferrite (x?=?0.2) (~4.3?×?10^-9 A^-1m) compared to normal compacted (NC) unsubstituted cobalt ferrite (~0.8?×?10^-9 A^-1m).

SUBMITTER: Reddy MV

PROVIDER: S-EPMC5554159 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Colossal piezomagnetic response in magnetically pressed Zr+4 substituted cobalt ferrites.

Reddy Monaji Vinitha MV Lisfi Abdellah A Pokharel Sabin S Das Dibakar D

Scientific reports 20170811 1

A remarkable 111% increase in magnetostriction (λ) and 435% increase in strain sensitivity (dλ/dH) (compared to normally compacted (NC) unsubstituted CoFe2O4 (CFO)) of Zr+4 doped CFO sample, Co1.2Zr0.2Fe1.6O4, prepared by magnetic field assisted compaction, have been reported in this study. Magnetic field assisted compaction (MC) has been employed to process Zr-doped cobalt ferrites, Co1+xZrxFe<sub ...[more]

PMID: 28801628

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Project description:BackgroundIn vivo monitoring of cell biodistribution using positron emission tomography (PET) provides a quantitative non-invasive method to further optimize cell therapies and related new developments in the field. Our group has earlier optimized and evaluated the in vitro properties of two radiotracers,[89Zr]Zr-(oxinate)4 and [89Zr]Zr-DFO-NCS, for the radiolabelling of different cell types. Here, we performed a microPET study to assess the in vivo biodistribution of cells in rats using these two radiotracers. Human decidual stromal cells (hDSC) and rat macrophages (rMac) were radiolabelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS. Rats were intravenously injected with radiolabelled cells, and the in vivo biodistribution was monitored with microPET/CT imaging for up to day 7. Organ uptake was evaluated and presented as a percentage of injected activity per gram tissue (%IA/g) and total absorbed organ doses (mSv/MBq).ResultsThe biodistribution in vivo showed an immediate uptake in the lungs. Thereafter, [89Zr]Zr-(oxinate)4 labelled cells migrated to the liver, while the signal from [89Zr]Zr-DFO-NCS labelled cells lingered in the lungs. The differences in the in vivo behaviour for the same cell type appeared related to the radiotracer labelling. After 24 h, [89Zr]Zr-(oxinate)4 labelled cells had over 70% higher liver uptake for both hDSC and rMac compared to [89Zr]Zr-DFO-NCS labelled cells, whereas [89Zr]Zr-DFO-NCS labelled cells showed over 60% higher uptake in the lungs compared to [89Zr]Zr-(oxinate)4 labelled cells. This difference in both lung and liver uptake continued until day 7. Dosimetry calculations showed a higher effective dose (mSv/MBq) for [89Zr]Zr-DFO-NCS compared to [89Zr]Zr-(oxinate)4, for both cell types. Although the bone uptake was higher for [89Zr]Zr-(oxinate)4 labelled cells, the prolonged uptake in the lungs contributed to a significant crossfire to bone marrow resulting in a higher bone dose.ConclusionThe [89Zr]Zr-DFO-NCS labelled cells suggest a prolonged accumulation in the lungs, while [89Zr]Zr-(oxinate)4 suggests quicker clearance of the lungs followed by accumulation in the liver. Accumulation of radiolabelled cells in the liver corresponds to other cell-tracking methods. Further studies are required to determine the actual location of the [89Zr]Zr-DFO-NCS labelled cell.

Project description:BackgroundThere is a need to better characterise cell-based therapies in preclinical models to help facilitate their translation to humans. Long-term high-resolution tracking of the cells in vivo is often impossible due to unreliable methods. Radiolabelling of cells has the advantage of being able to reveal cellular kinetics in vivo over time. This study aimed to optimise the synthesis of the radiotracers [89Zr]Zr-oxine (8-hydroxyquinoline) and [89Zr]Zr-DFO-NCS (p-SCN-Bn-Deferoxamine) and to perform a direct comparison of the cell labelling efficiency using these radiotracers.ProceduresSeveral parameters, such as buffers, pH, labelling time and temperature, were investigated to optimise the synthesis of [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS in order to reach a radiochemical conversion (RCC) of >95 % without purification. Radio-instant thin-layer chromatography (iTLC) and radio high-performance liquid chromatography (radio-HPLC) were used to determine the RCC. Cells were labelled with [89Zr]Zr-oxine or [89Zr]Zr-DFO-NCS. The cellular retention of 89Zr and the labelling impact was determined by analysing the cellular functions, such as viability, proliferation, phagocytotic ability and phenotypic immunostaining.ResultsThe optimised synthesis of [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS resulted in straightforward protocols not requiring additional purification. [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS were synthesised with an average RCC of 98.4 % (n = 16) and 98.0 % (n = 13), respectively. Cell labelling efficiencies were 63.9 % (n = 35) and 70.2 % (n = 30), respectively. 89Zr labelling neither significantly affected the cell viability (cell viability loss was in the range of 1-8 % compared to its corresponding non-labelled cells, P value > 0.05) nor the cells' proliferation rate. The phenotype of human decidual stromal cells (hDSC) and phagocytic function of rat bone-marrow-derived macrophages (rMac) was somewhat affected by radiolabelling.ConclusionsOur study demonstrates that [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS are equally effective in cell labelling. However, [89Zr]Zr-oxine was superior to [89Zr]Zr-DFO-NCS with regard to long-term stability, cellular retention, minimal variation between cell types and cell labelling efficiency.

Project description:Multiple myeloma (MM) is a plasma B-cell hematologic cancer that causes significant skeletal morbidity. Despite improvements in survival, heterogeneity in response remains a major challenge in MM. Cluster of differentiation 38 (CD38) is a type II transmembrane glycoprotein overexpressed in myeloma cells and is implicated in MM cell signaling. Daratumumab is a U.S. Food and Drug Administration-approved high-affinity monoclonal antibody targeting CD38 that is clinically benefiting refractory MM patients. Here, we evaluated [89Zr]Zr-desferrioxamine (DFO)-daratumumab PET/CT imaging in MM tumor models. Methods: Daratumumab was conjugated to DFO-p-benzyl-isothiocyanate (DFO-Bz-NCS) for radiolabeling with 89Zr. Chelator conjugation was confirmed by electrospray ionization-mass spectrometry, and radiolabeling was monitored by instant thin-layer chromatography. Daratumumab was conjugated to Cyanine5 (Cy5) dye for cell microscopy. In vitro and in vivo evaluation of [89Zr]Zr-DFO-daratumumab was performed using CD38+ human myeloma MM1.S-luciferase (MM1.S) cells. Cellular studies determined the affinity, immunoreactivity, and specificity of [89Zr]Zr-DFO-daratumumab. A 5TGM1-luciferase (5TGM1)/KaLwRij MM mouse model served as control for imaging background noise. [89Zr]Zr-DFO-daratumumab PET/CT small-animal imaging was performed in severe combined immunodeficient mice bearing solid and disseminated MM tumors. Tissue biodistribution (7 d after tracer administration, 1.11 MBq/animal, n = 4-6/group) was performed in wild-type and MM1.S tumor-bearing mice. Results: A specific activity of 55.5 MBq/nmol (0.37 MBq/?g) was reproducibly obtained with [89Zr]Zr-daratumumab-DFO. Flow cytometry confirmed CD38 expression (>99%) on the surface of MM1.S cells. Confocal microscopy with daratumumab-Cy5 demonstrated specific cell binding. Dissociation constant, 3.3 nM (±0.58), and receptor density, 10.1 fmol/mg (±0.64), was obtained with a saturation binding assay. [89Zr]Zr-DFO-daratumumab/PET demonstrated specificity and sensitivity for detecting CD38+ myeloma tumors of variable sizes (8.5-128 mm3) with standardized uptake values ranging from 2.1 to 9.3. Discrete medullar lesions, confirmed by bioluminescence images, were efficiently imaged with [89Zr]Zr-DFO-daratumumab/PET. Biodistribution at 7 d after administration of [89Zr]Zr-DFO-daratumumab showed prominent tumor uptake (27.7 ± 7.6 percentage injected dose per gram). In vivo blocking was achieved with a 200-fold excess of unlabeled daratumumab. Conclusion: [89Zr]Zr-DFO- and Cy5-daratumumab demonstrated superb binding to CD38+ human MM cells and significantly low binding to CD38low cells. Daratumumab bioconjugates are being evaluated for image-guided delivery of therapeutic radionuclides.

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Colossal piezomagnetic response in magnetically pressed Zr⁺⁴ substituted cobalt ferrites.

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Colossal piezomagnetic response in magnetically pressed Zr<sup>+4</sup> substituted cobalt ferrites.

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