scholarly journals Cyclam-Based Chelators Bearing Phosphonated Pyridine Pendants for 64Cu-PET Imaging : Synthesis, Physico-Chemical Studies, Radiolabeling and Bioimaging.

Author(s):  
Richard Knighton ◽  
Thibault Troadec ◽  
Valerie Mazan ◽  
Patricia La Saëc ◽  
Séverine Marionneau-Lambot ◽  
...  

Herein we present the preparation of two novel cyclam-based macrocycles (te1pyp and cb-te1pyp), bearing phosphonate-appended pyridine side-arms for the coordination of copper(II) ions in the context of 64Cu PET imaging. The two ligands have been prepared through conventional protection-alkylation sequences on cyclam, and their coordination properties have been thoroughly investigated. The corresponding copper complexes have been fully characterized in the solid-state (X-Ray diffraction analysis) and in solution (EPR and UV-Vis spectroscopies). Potentiometric studies, combined with spectrometry, have also allowed us to determine their thermodynamic stability constants, confirming their high affinity for copper(II) cations. The kinetic inertness of the complexes has also been verified by acid-assisted dissociation experiments, enabling their use in 64Cu-PET imaging in mice for the first time. Indeed, the two ligands could be quantitatively radiolabeled under mild conditions, and the resulting 64Cu complexes have demonstrated excellent stability in serum. PET imaging demon-strated a set of features emerging from the combination of picolinates and phosphonate units: high stability in vivo, fast clear-ance from the body via renal elimination, and most interestingly, very low fixation in the liver. The latter is in contrast with what was observed for monopicolinate cyclam (te1pa), that had a non-negligible accumulation in the liver, owing probably to its different charge and lipophillicity. These results thus pave the way for the use of such phosphonated pyridine chelators for in vivo 64Cu-PET imaging.

2020 ◽  
Author(s):  
Richard Knighton ◽  
Thibault Troadec ◽  
Valerie Mazan ◽  
Patricia La Saëc ◽  
Séverine Marionneau-Lambot ◽  
...  

Herein we present the preparation of two novel cyclam-based macrocycles (te1pyp and cb-te1pyp), bearing phosphonate-appended pyridine side-arms for the coordination of copper(II) ions in the context of 64Cu PET imaging. The two ligands have been prepared through conventional protection-alkylation sequences on cyclam, and their coordination properties have been thoroughly investigated. The corresponding copper complexes have been fully characterized in the solid-state (X-Ray diffraction analysis) and in solution (EPR and UV-Vis spectroscopies). Potentiometric studies, combined with spectrometry, have also allowed us to determine their thermodynamic stability constants, confirming their high affinity for copper(II) cations. The kinetic inertness of the complexes has also been verified by acid-assisted dissociation experiments, enabling their use in 64Cu-PET imaging in mice for the first time. Indeed, the two ligands could be quantitatively radiolabeled under mild conditions, and the resulting 64Cu complexes have demonstrated excellent stability in serum. PET imaging demon-strated a set of features emerging from the combination of picolinates and phosphonate units: high stability in vivo, fast clear-ance from the body via renal elimination, and most interestingly, very low fixation in the liver. The latter is in contrast with what was observed for monopicolinate cyclam (te1pa), that had a non-negligible accumulation in the liver, owing probably to its different charge and lipophillicity. These results thus pave the way for the use of such phosphonated pyridine chelators for in vivo 64Cu-PET imaging.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shreeya Sriram ◽  
Shitij Avlani ◽  
Matthew P. Ward ◽  
Shreyas Sen

AbstractContinuous multi-channel monitoring of biopotential signals is vital in understanding the body as a whole, facilitating accurate models and predictions in neural research. The current state of the art in wireless technologies for untethered biopotential recordings rely on radiative electromagnetic (EM) fields. In such transmissions, only a small fraction of this energy is received since the EM fields are widely radiated resulting in lossy inefficient systems. Using the body as a communication medium (similar to a ’wire’) allows for the containment of the energy within the body, yielding order(s) of magnitude lower energy than radiative EM communication. In this work, we introduce Animal Body Communication (ABC), which utilizes the concept of using the body as a medium into the domain of untethered animal biopotential recording. This work, for the first time, develops the theory and models for animal body communication circuitry and channel loss. Using this theoretical model, a sub-inch$$^3$$ 3 [1″ × 1″ × 0.4″], custom-designed sensor node is built using off the shelf components which is capable of sensing and transmitting biopotential signals, through the body of the rat at significantly lower powers compared to traditional wireless transmissions. In-vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation $$>99\%$$ > 99 % when compared to traditional wireless communication modalities, with a 50$$\times$$ × reduction in power consumption.


Energies ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 1230
Author(s):  
Jessica Manzi ◽  
Annalisa Paolone ◽  
Oriele Palumbo ◽  
Domenico Corona ◽  
Arianna Massaro ◽  
...  

In this manuscript, we report a detailed physico-chemical comparison between the α- and β-polymorphs of the NaMnO2 compound, a promising material for application in positive electrodes for secondary aprotic sodium batteries. In particular, the structure and vibrational properties, as well as electrochemical performance in sodium batteries, are compared to highlight differences and similarities. We exploit both laboratory techniques (Raman spectroscopy, electrochemical methods) and synchrotron radiation experiments (Fast-Fourier Transform Infrared spectroscopy, and X-ray diffraction). Notably the vibrational spectra of these phases are here reported for the first time in the literature as well as the detailed structural analysis from diffraction data. DFT+U calculations predict both phases to have similar electronic features, with structural parameters consistent with the experimental counterparts. The experimental evidence of antisite defects in the beta-phase between sodium and manganese ions is noticeable. Both polymorphs have been also tested in aprotic batteries by comparing the impact of different liquid electrolytes on the ability to de-intercalated/intercalate sodium ions. Overall, the monoclinic α-NaMnO2 shows larger reversible capacity exceeding 175 mAhg−1 at 10 mAg−1.


2011 ◽  
Vol 170 ◽  
pp. 165-169 ◽  
Author(s):  
Tahir Ali ◽  
Ernst Bauer ◽  
Gerfried Hilscher ◽  
Herwig Michor

We report on structural and superconducting properties of La3-xRxNi2B2N3- where La is substituted by the magnetic rare-earth elements Ce, Pr, Nd. The compounds Pr3Ni2B2N3- and Nd3Ni2B2N3- are characterized for the first time. Powder X-ray diffraction confirmed all samples R3Ni2B2N3- with R = La, Ce, Pr, Nd and their solid solutions to crystallize in the body centered tetragonal La3Ni2B2N3 structure type. Superconducting and magnetic properties of La3-xRxNi2B2N3- were studied by resistivity, specific heat and susceptibility measurements. While La3Ni2B2N3- has a superconducting transition temperature Tc ~ 14 K, substitution of La by Ce, Pr, and Nd leads to magnetic pair breaking and, thus, to a gradual suppression of superconductivity. Pr3Ni2B2N3- exibits no long range magnetic order down to 2 K, Nd3Ni2B2N3- shows ferrimagnetic ordering below TC =17 K and a spin reorientation transition to a nearly antiferromagnetic state at 10 K.


Author(s):  
Abou-eisha A ◽  
Adel E El-din

Objective: The aim of this study was to investigate, for the first time, the possible in vivo genotoxic and carcinogenic activity associated with exposure to norgestrel (NGT) drug through employing the very recently established and adjusted genotoxic and tumorigenic methods in Drosophila melanogaster.Methods: Two in vivo genotoxic test systems were used; one detects the somatic mutation and recombination effects (somatic mutation and recombination test [SMART] wing-spot test) and the other detects the primary DNA damage (the comet test) in the body cells of D. melanogaster. On the other hand, the warts (wts)-based SMART assay is a vital genetic examination in Drosophila used to identify and characterize cancer potential of compounds.Results: Four experimental doses of NGT were used (ranging from 0.24 μM to 16 μM). NGT was found to be non-genotoxic at all tested concentrations even at the highest dose level 16 μM and failed to increase the frequency of tumors in the somatic cells of D. melanogaster.Conclusion: Our results strengthen the hypothesis that steroidal drugs might act through a non-genotoxic carcinogen mechanism where the carcinogenic properties occur by direct stimulation of cellular proliferation through a steroid receptor-mediated mechanism. In addition, the results obtained in this research work may contribute to highlighting the importance of NGT as a potent neuroprotective antioxidant drug.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1880-1880
Author(s):  
Georg Seifert ◽  
Patrick Jesse ◽  
Aram Prokop ◽  
Tobias Reindl ◽  
Stephan Lobitz ◽  
...  

Abstract Mistletoe (Viscum album) is one of the most used alternative cancer therapies applied as monotherapy or in combination with conventional therapies. Anti-tumor effects of mistletoe (MT) extracts were related to cytostatic and immunomodulatory effects observed in vitro. Aqueous MT extracts contain the three mistletoe lectins I, II and III as one predominant group of biologically active agents. The MT lectins inhibit protein biosynthesis by inactivating the 60S ribosomal subunit. Mistletoe lectin-I (ML-I) is one important apoptosis inducing compound. It is a heterodimer that consists of a cytotoxic A-chain (ribosome inactivating protein, RIP type 1) linked by a carbohydrate binding B-chain for cellular lectin uptake. However, although MT is widely used, there is a lack of scientific preclinical and clinical data. Here, we describe for the first time efficacy and mechanism of MT extracts against lymphoblastic leukemia in vitro and in vivo. For this purpose, we first investigated both the cytotoxic effect and mechanism of action of two standardized aqueous MT extracts (MT obtained from fir trees (MT-A); MT obtained from pine trees (MT-P)) and isolated ML-I, in three human acute lymphoblastic leukemia (ALL) cell lines (NALM-6, sup-B-15 and REH). MT-A, MT-P and ML-I clearly inhibited cell proliferation as determined by LDH reslease assays at very low concentrations (ML-I LD50 from 0,05 ng/ml to 10 ng/ml depending on the host tree) with MT-P being the most cytotoxic extract. The mechanism of cell death was determined by DNA-fragmentation assays. These indicated dose dependent induction of apoptosis as the main mechanism of cell death. Finally, we evaluated the efficacy of MT-A and MT-P in an in vivo SCID-model of pre-B ALL (NALM-6). For this purpose, mice (n=8/group) were injected i.v. with 1 × 106NALM6 cells and treated by intraperitoneal injections four times per week for 3 weeks (day 1–4; 7–11; 14–18) at varying doses (1, 5 and 50 mg/Kg (plant weight/body weight)). Mice (n=8) treated with PBS and cyclophosphamide (100 mg/kg, once on day 1) were used as negative and positive controls, respectively. Toxicity, peripheral blood counts, bodyweight and survival was determined over time. Interestingly, both MT extracts in all tested concentrations significantly improved survival (up to 55,4 days) in contrast to controls (34,6 days). Furthermore, no hematologic side effects were observed from this treatment as indicated by completely stable blood counts. Also the body weight of treated animals remained stable over time indicating a complete absence of systemic toxicity in the selected dose range. In summary, we demonstrate for the first time efficacy and mechanism of MT extracts against ALL in vitro and in vivo and hereby provide an important base line for the design of clinical trials with these compounds.


2020 ◽  
Author(s):  
Kyung Oh Jung ◽  
Young-Hwa Kim ◽  
Seock-Jin Chung ◽  
Keon Wook Kang ◽  
Siyeon Rhee ◽  
...  

Clinically, there has been significant interest in the use of exosomes for diagnostic applications as promising biomarkers and therapeutic applications as therapeutic vehicles. However, knowledge of in vivo physiological biodistribution of exosomes was difficult to assess until now. Physiological distribution of exosomes in the body must be elucidated for clinical application. In this study, we aimed to develop reliable and novel methods to monitor biodistribution of exosomes using in vivo PET and optical imaging.MethodsExosomes were isolated from cultured medium of 4T1, mouse breast cancer cells. Exosomes were labeled with Cy7 and 64Cu (or 68Ga). In mice, radio/fluorescent dye-labeled exosomes were injected through the lymphatic routes (footpad injection) and hematogenous metastatic routes (tail vein injection). Fluorescence and PET images were obtained and quantified. Radio-activity of ex vivo organs was measured by gamma counter.ResultsPET signals from exosomes in the lymphatic metastatic route were observed in the draining lymph nodes, which are not distinguishable with optical imaging. Immunohistochemistry revealed greater uptake of exosomes in brachial and axillary lymph nodes than inguinal lymph node. After administration through the hematogenous metastasis pathway, accumulation of exosomes was clearly observed in PET images in the lungs, liver, and spleen, showing results similar to ex vivo gamma counter data.ConclusionExosomes from tumor cells were successfully labeled with 64Cu (or 68Ga) and visualized by PET imaging. These results suggest that this cell type-independent, quick, and easy exosome labeling method using PET isotopes could provide valuable information for further application of exosomes in the clinic.


2015 ◽  
Vol 1721 ◽  
Author(s):  
A. B. Brune ◽  
W.T. Petuskey

ABSTRACTMechanical properties and new morphological data on synthetic sodium hydrogen urate monohydrate are reported and interpreted. Crystals formed in supersaturated aqueous solutions were identified by powder x-ray diffraction. Intact grains and separate needles were examined by several microscopy techniques, some reported here for the first time. The dominant morphology was spherulite-type, comprising tapered, branched blades (needles) radiating out of a common core. The pointed blade tips were truncated by (011) planes, corresponding to hydrogen-bonded planes. Branching was at about a 5° angle or its multiples, suggesting it accommodated by dislocation arrays at the low angle boundaries, as is often seen in twinning. Vicker’s micro-hardness, extrapolated to zero porosity, was 0.90 GPa, which is greater than the hardness measured by nano-indentation. Present results are anticipated to be useful in interpreting the mechanical characteristics of the material crystallized in vivo and its action concerning gout, and affording inferences on the role of the milieu on morphologies, fragmentation, and hardness.


2017 ◽  
Vol 10 (06) ◽  
pp. 1742002 ◽  
Author(s):  
Irina V. Kabakova ◽  
YuChen Xiang ◽  
Carl Paterson ◽  
Peter Török

Brillouin imaging (BI) for micromechanical characterization of tissues and biomaterials is a fast-developing field of research with a strong potential for medical diagnosis of disease-modified tissues and cells. Although the principles of BI imply its compatibility with in vivo and in situ measurements, the integration of BI with a flexible catheter, capable of reaching the region of interest within the body, is yet to be reported. Here, for the first time, we experimentally investigate integration of the Brillouin spectroscope with standard optical fiber components to achieve a Brillouin endoscope. The performance of single-fiber and dual-fiber endoscopes are demonstrated and analyzed. We show that a major challenge in construction of Brillouin endoscopes is the strong backward Brillouin scattering in the optical fiber and we present a dual-fiber geometry as a possible solution. Measurements of Brillouin spectra in test liquids (water, ethanol and glycerol) are demonstrated using the dual-fiber endoscope and its performance is analyzed numerically with the help of a beam propagation model.


Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 634 ◽  
Author(s):  
Marziyeh Ajdary ◽  
Mohammad Moosavi ◽  
Marveh Rahmati ◽  
Mojtaba Falahati ◽  
Mohammad Mahboubi ◽  
...  

Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.


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