Gamma-Camera Direct Imaging of the Plasma and On/Intra Cellular Distribution of the 99mTc-DPD-Fe3O4 Dual-Modality Contrast Agent in Peripheral Human Blood

The radiolabeled iron oxide nanoparticles constitute an attractive choice to be used as dual-modality contrast agents (DMCAs) in nuclear medical diagnosis, due to their ability to combine the benefits of two imaging modalities, for instance single photon emission computed tomography (SPECT) with magnetic resonance imaging (MRI). Before the use of any DMCA, the investigation of its plasma extra- and on/intra cellular distribution in peripheral human blood is of paramount importance. Here, we focus on the in vitro investigation of the distribution of 99mTc-DPD-Fe3O4 DMCA in donated peripheral human blood (the ligand 2-3-dicarboxypropane-1-1-diphosphonic-acid is denoted as DPD). Initially, we described the experimental methods we performed for the radiosynthesis of the 99mTc-DPD-Fe3O4, the preparation of whole blood and blood plasma samples, and their incubation conditions with 99mTc-DPD-Fe3O4. More importantly, we employed a gamma-camera apparatus for the direct imaging of the 99mTc-DPD-Fe3O4-loaded whole blood and blood plasma samples when subjected to specialized centrifugation protocols. The direct comparison of the gamma-camera data obtained at the exact same samples before and after their centrifugation enabled us to clearly identify the distribution of the 99mTc-DPD-Fe3O4 in the two components, plasma and cells, of peripheral human blood

A Novel Metal-Based Imaging Probe for Targeted Dual-Modality SPECT/MR Imaging of Angiogenesis

Superparamagnetic iron oxide nanoparticles with well-integrated multimodality imaging properties have generated increasing research interest in the past decade, especially when it comes to the targeted imaging of tumors. Bevacizumab (BCZM) on the other hand is a well-known and widely applied monoclonal antibody recognizing VEGF-A, which is overexpressed in angiogenesis. The aim of this proof-of-concept study was to develop a dual-modality nanoplatform for in vivo targeted single photon computed emission tomography (SPECT) and magnetic resonance imaging (MRI) of tumor vascularization. Iron oxide nanoparticles (IONPs) have been coated with dimercaptosuccinic acid (DMSA), for consequent functionalization with the monoclonal antibody BCZM radiolabeled with 99mTc, via well-developed surface engineering. The IONPs were characterized based on their size distribution, hydrodynamic diameter and magnetic properties. In vitro cytotoxicity studies showed that our nanoconstruct does not cause toxic effects in normal and cancer cells. Fe3O4-DMSA-SMCC-BCZM-99mTc were successfully prepared at high radiochemical purity (>92%) and their stability in human serum and in PBS were demonstrated. In vitro cell binding studies showed the ability of the Fe3O4-DMSA-SMCC-BCZM-99mTc to bind to the VEGF-165 isoform overexpressed on M-165 tumor cells. The ex vivo biodistribution studies in M165 tumor-bearing SCID mice showed high uptake in liver, spleen, kidney and lungs. The Fe3O4-DMSA-SMCC-BCZM-99mTc demonstrated quick tumor accumulation starting at 8.9 ± 1.88%ID/g at 2 h p.i., slightly increasing at 4 h p.i. (16.21 ± 2.56%ID/g) and then decreasing at 24 h p.i. (6.01 ± 1.69%ID/g). The tumor-to-blood ratio reached a maximum at 24 h p.i. (~7), which is also the case for the tumor-to-muscle ratio (~18). Initial pilot imaging studies on an experimental gamma-camera and a clinical MR camera prove our hypothesis and demonstrate the potential of Fe3O4-DMSA-SMCC-BCZM-99mTc for targeted dual-modality imaging. Our findings indicate that Fe3O4-DMSA-SMCC-BCZM-99mTc IONPs could serve as an important diagnostic tool for biomedical imaging as well as a promising candidate for future theranostic applications in cancer

99mTc-Labeled Iron Oxide Nanoparticles as Dual-Modality Contrast Agent: A Preliminary Study from Synthesis to Magnetic Resonance and Gamma-Camera Imaging in Mice Models

The combination of two imaging modalities in a single agent has received increasing attention during the last few years, since its synergistic action guarantees both accurate and timely diagnosis. For this reason, dual-modality contrast agents (DMCAs), such as radiolabeled iron oxide (namely Fe3O4) nanoparticles, constitute a powerful tool in diagnostic applications. In this respect, here we focus on the synthesis of a potential single photon emission computed tomography/magnetic resonance imaging (SPECT/MRI) DMCA, which consists of Fe3O4 nanoparticles, surface functionalized with 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD) and radiolabeled with 99mTc, [99mTc]Tc-DPD-Fe3O4. The in vitro stability results showed that this DMCA is highly stable after 24 h of incubation in phosphate buffer saline (~92.3% intact), while it is adequately stable after 24 h of incubation with human serum (~67.3% intact). Subsequently, [99mTc]Tc-DPD-Fe3O4 DMCA was evaluated in vivo in mice models through standard biodistribution studies, MR imaging and gamma-camera imaging. All techniques provided consistent results, clearly evidencing noticeable liver uptake. Our work documents that [99mTc]Tc-DPD-Fe3O4 has all the necessary characteristics to be a potential DMCA

Gallium-68 Labeled Iron Oxide Nanoparticles Coated with 2,3-Dicarboxypropane-1,1-diphosphonic Acid as a Potential PET/MR Imaging Agent: A Proof-of-Concept Study

The aim of this study was to develop a dual-modality PET/MR imaging probe by radiolabeling iron oxide magnetic nanoparticles (IONPs), surface functionalized with water soluble stabilizer 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), with the positron emitter Gallium-68. Magnetite nanoparticles (Fe3O4 MNPs) were synthesized via coprecipitation method and were stabilized with DPD. The Fe3O4-DPD MNPs were characterized based on their structure, morphology, size, surface charge, and magnetic properties. In vitro cytotoxicity studies showed reduced toxicity in normal cells, compared to cancer cells. Fe3O4-DPD MNPs were successfully labeled with Gallium-68 at high radiochemical purity ( GT 91%) and their stability in human serum and in PBS was demonstrated, along with their further characterization on size and magnetic properties. The ex vivo biodistribution studies in normal Swiss mice showed high uptake in the liver followed by spleen. The acquired PET images were in accordance with the ex vivo biodistribution results. Our findings indicate that 68 Ga-Fe3O4-DPD MNPs could serve as an important diagnostic tool for biomedical imaging

Pronounced and reversible modulation of the piezoelectric coefficients by a low magnetic field in a magnetoelectric PZT-5%Fe3O4 system

Composite magnetoelectric compounds that combine ferroelectricity/piezoelectricity and ferromagnetism/magnetostriction are investigated intensively for room-temperature applications. Here, we studied bulk composites of a magnetostrictive constituent, ferromagnetic Fe 3 O 4 nanoparticles, homogeneously embedded in a ferroelectric/piezoelectric matrix, Pb(Zr 0.52 Ti 0.48 )O 3 (PZT). Specifically, we focused on PZT-5%Fe 3 O 4 samples which are strongly insulating and thus sustain a relatively high out-of-plane external electric field, E ex,z . The in-plane strain-electric field curve (S(E ex,z )) was carefully recorded upon successive application and removal of an out-of-plane external magnetic field, H ex,z . The obtained S(E ex,z ) data exhibited two main features. First, the respective in-plane piezoelectric coefficients, d(E ex,z ) = 200-250 pm/V, show a dramatic decrease, 50-60%, upon application of a relatively low H ex,z = 1 kOe. Second, the process is completely reversible since the initial value of d(E ex,z ) is recovered upon removal of H ex,z . Polarization data, P(E ex,z ), evidenced that the Fe 3 O 4 nanoparticles introduced static structural disorder that made PZT harder. Taken together, these results prove that the Fe 3 O 4 nanoparticles, except for static structural disorder, introduce reconfigurable magnetic disorder that modifies the in-plane S(E ex,z ) curve and the accompanying d(E ex,z ) of PZT when an external magnetic field is applied at will. The room-temperature feasibility of these findings renders the PZT-x%Fe 3 O 4 system a solid basis for the development of magnetic-field-controlled PE devices

Degradation of the remanent ferromagnetic state under the action of ferroelectric relaxation processes in Co/(1-x)PMN-xPT/Co hybrids: Possible implications on cryogenic and room-temperature applications

Low-dimensional hybrid structures of heterogeneous constituents usually exhibit abnormal properties, a fact that makes such hybrids attractive for various cryogenic and room-temperature applications. Here, we studied Co/(1 - x)Pb(Mg 1/3 Nb 2/3 )O 3 -xPbTiO 3 /Co (Co/PMN-xPT/Co) with x=0.29 and 0.30, specifically focusing on the evolution of the remanent ferromagnetic state, m rem of the Co outer layers in the whole temperature range from 300K down to 10K, upon application of an external electric field, E ex . We observed that m rem was vulnerable to degradation through the occurrence of electric field-induced magnetic instabilities (EMIs) that appeared only when E ex ≠0kV/cm and were facilitated as E ex increases. However, EMIs completely ceased below a characteristic temperature T ces =170K even for the maximum |E ex |=5kV/cm applied in this work. A direct comparison of the magnetization data of the Co/PMN-xPT/Co hybrids reported here with the electromechanical properties of the parent PMN-xPT crystals plausibly indicates that EMIs are motivated by the coupling of the ferromagnetic domains of the Co outer layers with the ferroelectric domains of the PMN-xPT crystal. These results highlight the drawback of EMIs in relevant hybrids and delimit the temperature regime for the reliable operation of the Co/PMN-xPT/Co ones studied here

Mixed orbital states and modulated crystal structures in La1−x Ca x MnO3 deduced from synchrotron X-ray diffraction

Abstract In the model manganese perovskites La1−x Ca x MnO3, several important phenomena have been observed, including ferromagnetic metallic/insulating states, colossal magnetoresistance effects, and charge- and orbital-ordered states. In the past, only compounds with x = 1/2, 2/3 and 3/4 and an insulating ground/antiferromagnetic state have been studied. To fully understand the crystal and electronic structures of these materials, it is important to study compounds with doping levels in the range of 0.5 < x < 2/3. Here we study the crystal structure in a series of compounds with 0.5 < x ≤ 0.6 using ultrahigh-resolution synchrotron X-ray diffraction. The experimental results reveal that all compounds undergo a structural transition at T < T CO(x) ≈ 200 − 220 K with the concomitant emergence of superlattice Bragg peaks, which can be indexed assuming a superstructure with a modulation propagation vector, τ. At the base temperature of 5 K, the modulation vector of the superstructure τ = [τ a , 0, 0] is parallel to the a-axis, with τ a varying linearly with x, as τ a  ≈ 1 − x. Our results may aid attempts to understand more deeply phenomena related to spin, charge, and orbital ordering, as well as colossal magnetoresistance and symmetry breaking and emergent order in quantum states