Extent of Pseudocapacitance in High‐Surface Area Vanadium Nitrides

Early transition‐metal nitrides, especially vanadium nitride (VN), have shown promise for use in high energy density supercapacitors due to their high electronic conductivity, areal specific capacitance, and ability to be synthesized in high surface area form. Their further development would benefit from an understanding of their pseudocapacitive charge storage mechanism. In this paper, the extent of pseudocapacitance exhibited by vanadium nitride in aqueous electrolytes was investigated using cyclic voltammetry and electrochemical impedance spectroscopy. The pseudocapacitance contribution to the total capacitance in the nitride material was much higher than the double‐layer capacitance and ranged from 85 % in basic electrolyte to 87 % in acidic electrolyte. The mole of electrons transferred per VN material during pseudocapacitive charge storage was also evaluated. This pseudocapacitive charge‐storage is the key component in the full utilization of the properties of early‐transition metal nitrides for high‐energy density supercapacitors.Double‐layer capacitance vs. pseudocapacitance: the electrostatic double‐layer and pseudocapacitive charge storage mechanisms in high‐surface‐area vanadium nitride are investigated. The magnitude of the pseudocapacitive charge storage capacity and mole of electrons transferred are reported. The pseudocapacitive charge‐storage mechanism is the key component in maximizing the energy density of supercapacitors based on transition‐metal nitrides.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146597/1/batt201800050.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146597/2/batt201800050_am.pd

99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy

PURPOSE: The purpose of this study was to determine the value of (99m)Tc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. METHODS: TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6-8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (DeltaU). RESULTS: In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean DeltaU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. DeltaU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum DeltaU in primary tumour and in the lymph nodes. CONCLUSIONS: Within the dose range of 0-8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic respons

Site-Specific Labeling of Annexin V with F-18 for Apoptosis Imaging

Annexin V is useful in detecting apoptotic cells by binding to phosphatidylserine (PS) that is exposed on the outer surface of the cell membrane during apoptosis. In this study, we examined the labeling of annexin V-128, a mutated form of annexin V that has a single cysteine residue at the NH2 terminus, with the thiol-selective reagent 18F-labeling agent N-[4-[(4-[18F]fluorobenzylidene)aminooxy]butyl]maleimide ([18F]FBABM). We also examined the cell binding affinity of the 18F-labeled annexin V-128 ([18F]FAN-128). [18F]FBABM was synthesized in two-step, one-pot method modified from literature procedure. (Toyokuni et al., Bioconjugate Chem. 2003, 14, 1253−1259). The average yield of [18F]FBABM was 23 ± 4% (n = 4, decay-corrected) and the specific activity was ∼6000 Ci/mmol. The total synthesis time was ∼92 min. The critical improvement of this study was identifying and then developing a purification method to remove an impurity N-[4-[(4-dimethylaminobenzylidene)aminooxy]butyl]maleimide 4, whose presence dramatically decreased the yield of protein labeling. Conjugation of [18F]FBABM with the thiol-containing annexin V-128 gave [18F]FAN-128 in 37 ± 9% yield (n = 4, decay corrected). Erythrocyte binding assay of [18F]FAN-128 showed that this modification of annexin V-128 did not compromise its membrane binding affinity. Thus, an in vivo investigation of [18F]FAN-128 as an apoptosis imaging agent is warranted

APOMAB®, a La-Specific Monoclonal Antibody, Detects the Apoptotic Tumor Response to Life-Prolonging and DNA-Damaging Chemotherapy

Background: Antineoplastic therapy may impair the survival of malignant cells to produce cell death. Consequently, direct measurement of tumor cell death in vivo is a highly desirable component of therapy response monitoring. We have previously shown that APOMAB® representing the DAB4 clone of a La/SSB-specific murine monoclonal autoantibody is a malignant cell-death ligand, which accumulates preferentially in tumors in an antigen-specific and dose-dependent manner after DNA-damaging chemotherapy. Here, we aim to image tumor uptake of APOMAB® (DAB4) and to define its biological correlates. Methodology/Principal Findings: Brisk tumor cell apoptosis is induced in the syngeneic EL4 lymphoma model after treatment of tumor-bearing mice with DNA-damaging cyclophosphamide/etoposide chemotherapy. Tumor and normal organ accumulation of Indium 111 (111In)-labeled La-specific DAB4 mAb as whole IgG or IgG fragments was quantified by whole-body static imaging and organ assay in tumor-bearing mice. Immunohistochemical measurements of tumor caspase-3 activation and PARP-1 cleavage, which are indicators of early and late apoptosis, respectively, were correlated with tumor accumulation of DAB4. Increased tumor accumulation of DAB4 was associated directly with both the extent of chemotherapy-induced tumor cell death and DAB4 binding per dead tumor cell. Tumor DAB4 accumulation correlated with cumulative caspase-3 activation and PARP-1 cleavage as tumor biomarkers of apoptosis and was directly related to the extended median survival time of tumor-bearing mice. Conclusions/Significance: Radiolabeled La-specific monoclonal antibody, DAB4, detected dead tumor cells after chemotherapy, rather than chemosensitive normal tissues of gut and bone marrow. DAB4 identified late apoptotic tumor cells in vivo. Hence, radiolabeled DAB4 may usefully image responses to human carcinoma therapy because DAB4 would capture the protracted cell death of carcinoma. We believe that the ability of radiolabeled DAB4 to rapidly assess the apoptotic tumor response and, consequently, to potentially predict extended survival justifies its future clinical development as a radioimmunoscintigraphic agent. This article is part I of a two-part series providing proof-of-concept for the the diagnostic and therapeutic use of a La-specific monoclonal antibody, the DAB4 clone of which is represented by the registered trademark, APOMAB®.Fares Al-Ejeh, Jocelyn M. Darby, Chris Tsopelas, Douglas Smyth, Jim Manavis and Michael P. Brow

Phosphatidylserine targeting for diagnosis and treatment of human diseases

Cells are able to execute apoptosis by activating series of specific biochemical reactions. One of the most prominent characteristics of cell death is the externalization of phosphatidylserine (PS), which in healthy cells resides predominantly in the inner leaflet of the plasma membrane. These features have made PS-externalization a well-explored phenomenon to image cell death for diagnostic purposes. In addition, it was demonstrated that under certain conditions viable cells express PS at their surface such as endothelial cells of tumor blood vessels, stressed tumor cells and hypoxic cardiomyocytes. Hence, PS has become a potential target for therapeutic strategies aiming at Targeted Drug Delivery. In this review we highlight the biomarker PS and various PS-binding compounds that have been employed to target PS for diagnostic purposes. We emphasize the 35 kD human protein annexin A5, that has been developed as a Molecular Imaging agent to measure cell death in vitro, and non-invasively in vivo in animal models and in patients with cardiovascular diseases and cancer. Recently focus has shifted from diagnostic towards therapeutic applications employing annexin A5 in strategies to deliver drugs to cells that express PS at their surface

Titanium dioxide nanotube films for electrochemical supercapacitors: biocompatibility and operation in an electrolyte based on a physiological fluid

Growing interest in developing devices that can be implantable or wearable requires the identification of suitable materials for the components of these devices. Electrochemical supercapacitors are not the exception in this trend, and identifying electrode materials that can be not only suitable for the capacitive device but also biocompatible at the same time is important. In addition, it would be advantageous if physiological fluids could be used instead of more conventional (and often corrosive) electrolytes for implantable or wearable supercapacitors. In this study, we assess the biocompatibility of films of anodized TiO2 nanotubes subjected to the subsequent annealing in Ar atmosphere and evaluate their capacitive performance in a physiological liquid. A biocompatibility test tracking cell proliferation on TiO2 nanotube electrodes and electrochemical tests in 0.01 M phosphate-buffered saline solution are discussed. It is expected that the study will stimulate further developments in this area