Tetramethylene Phosphonate Research Articles

Influence of Several Phosphate-Containing Additives on the Stability and Electrochemical Behavior of Positive Electrolytes for Vanadium Redox Flow Battery

The poor operational stability of electrolytes is a persistent impediment in building redox flow battery technology; choosing suitable stability additives is usually the research direction to solve this problem. The effects of five phosphate containing additives (including 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP), hexamethylene diamine tetramethylene phosphonic acid (HDTMPA), amino trimethylene phosphonic acid (ATMPA), sodium ethylenediamine tetramethylene phosphonate (EDTMPS), and diethyl triamine pentamethylene phosphonic acid (DTPMP)) on the thermal stability and electrochemical performance of the positive electrolyte of vanadium redox flow battery were investigated. With 0.5 wt% addition, most of the selected additives were able to improve the thermal stability of the electrolyte. HEDP and HDTMPA extended the stability time of the pentavalent vanadium electrolyte at 50 °C from 5 days (blank sample) to 30 days and 15 days, respectively. The electrochemical performance of the electrolyte was further investigated by cyclic voltammetry, steady state polarization, and electrochemical impedance spectroscopy tests. It was found that most of the additives enhanced the electrochemical activity of the positive electrolyte, and the diffusion coefficients, exchange current densities, and reaction rate constants of V(IV) species became larger with the addition of these additives. It is verified that the thermal stability and electrochemical stability of the electrolyte are significantly improved by the combination of ATMPA + HEDP or ATMPA + HDTMPA. This study provides a new approach to improve the stability of the positive electrolyte for vanadium redox flow battery.

Novel organophosphonate-decorated WS2 nanosheets towards flame retardancy and mechanical enhancement of epoxy resin

By noncovalently surface-modifying 2D WS2 nanosheets (WC) with in situ generated iron ethylenediamine tetramethylene phosphonate (FeP), novel organophosphonate-decorated nanosheets (WC@FeP) were designed and prepared. Combining the physical barrier effects of WC nanosheets with the catalytic charring activity of FeP, WC@FeP improved the flame retardancy of the epoxy resin (EP), including heat inhibition and smoke suppression. Compared with those of neat EP, the EP composites containing 8 wt% of the WC@FeP (EP/8WC@FeP) passed a UL94 V-0 rating with a LOI value increased from 22.5 to 29.5 vol%. Furthermore, the peak heat release rate (PHRR), total heat release rate (THR), and total smoke release (TSP) of EP/8WC@FeP were remarkably reduced by 58.2%, 25.1%, and 44.5%, respectively. In addition, thanks to the large aspect ratio of the decorated nanosheets with flexible-but-tough nature, WC@FeP effectively enhanced the mechanical properties of the composites, in which the tensile strength and modulus of EP/8WC@FeP were enhanced by 23% and 24%, respectively, without sacrificing the toughness. Taking advantage of these features, the surface organo-decoration of 2D nanosheets broadens their applications in polymeric materials.

Stability, dissolution, and cytotoxicity of NaYF4-upconversion nanoparticles with different coatings

Upconversion nanoparticles (UCNPs) have attracted considerable attention owing to their unique photophysical properties. Their utilization in biomedical applications depends on the understanding of their transformations under physiological conditions and their potential toxicity. In this study, NaYF4:Yb,Er UCNPs, widely used for luminescence and photophysical studies, were modified with a set of four different coordinatively bound surface ligands, i.e., citrate, alendronate (AA), ethylendiamine tetra(methylene phosphonate) (EDTMP), and poly(maleic anhydride-alt-1-octadecene) (PMAO), as well as silica coatings with two different thicknesses. Subsequently, the aging-induced release of fluoride ions in water and cell culture media and their cytotoxic profile to human keratinocytes were assessed in parallel to the cytotoxic evaluation of the ligands, sodium fluoride and the lanthanide ions. The cytotoxicity studies of UCNPs with different surface modifications demonstrated the good biocompatibility of EDTMP-UCNPs and PMAO-UCNPs, which is in line with the low amount of fluoride ions released from these samples. An efficient prevention of UCNP dissolution and release of cytotoxic ions, as well as low cytotoxicity was also observed for UCNPs with a sufficiently thick silica shell. Overall, our results provide new insights into the understanding of the contribution of surface chemistry to the stability, dissolution behavior, and cytotoxicity of UCNPs. Altogether, the results obtained are highly important for future applications of UCNPs in the life sciences and bioimaging studies.

Functionalizing mesoporous silica with a nano metal–organic phosphonate towards mechanical‐robust, thermal‐resistant, and fire‐safety epoxy resin

AbstractEpoxy resin (EP) has featured many industrial and practical applications, but was plagued by its inherent flammability. Herein, a hybrid flame retardant (mSiO2@TETP) was fabricated by in‐situ immobilizing tin ethylenediamine tetramethylene phosphonate (TETP) on the mesoporous silica (mSiO2) surface, and was used to prepare mechanical‐robust, flame‐retardant, and thermal‐resistant EP composites. It is found that the introduction of only 1.0 wt% mSiO2@TETP into EP leads to a 20.5%, 19.7%, and 12.8% incremental tensile modulus, tensile strength, and impact strength, respectively. The EP composite with 5.0 wt% mSiO2@TETP (EP/mSiO2@TETP‐5) succeeds to the UL‐94 V‐0 grade, with a limiting oxygen index value of 29.0%. And the peak heat release rate, total heat release, peak smoke production rate, total smoke release, and peak CO production rate of EP/mSiO2@TETP‐5 decrease by 54.0%, 52.1%, 53.9%, 51.1%, and 55.7%, respectively in contrast with the values of pure EP. Moreover, the introduction of mSiO2@TETP results in an improvement in both the charring capacity and the initial thermal resistance (an increment in the glass transition temperature) of EP.

The radio-europium impurities in [153Sm]-EDTMP production: a review of isolation methods.

Many human cancers predominantly metastasize to the bone which causes bone pain and other symptoms. However, the management of bone metastases is challenging. Radionuclide therapy using low-energy beta-emitting radionuclides has yielded encouraging results. The aim of this therapy is to deliver the maximum dose to the metastatic sites but a minimal dose to the normal tissue. Samarium-153 [153Sm]Sm-Ethylenediamine tetramethylene phosphonate (EDTMP) is an FDA and European Medicine Agency approved (Quadramet) radionuclide and is widely used for bone pain palliation. 153Sm is reactor produced, and the presence of europium impurities is thus unavoidable. This in turn causes an increase in the hospital radioactive waste burden and in radiation absorbed doses to the patients, and therefore it is a concern. The effective removal of these impurities is thus highly desirable before its administration to the patients. In this article, we present a detailed review of the various methods described in the literature for separation of 153Sm and Eu, that is solvent extraction, ion-exchange chromatography, electrochromatography, electrochemical separation and supported ionic liquid phase.

Facile synthesis of carbon microspheres/tin ethylenediamine tetramethylene phosphonate hybrid for improving the mechanical, flame‐retardant, and thermal properties of epoxy resin

A botryoidal carbon microspheres/tin ethylenediamine tetramethylene phosphonate hybrid (CMS@TETP) was fabricated via a self‐assembly method and was applied to modify epoxy resin (EP) in order to simultaneously improve its mechanical, flame‐retardant, and thermal properties. The mechanical tests' results show that the addition of 1.0 wt% CMS@TETP endows EP with an increase in tensile and impact strengths of 24.4% and 23.1%, respectively, relative to the values of pure EP. The cone calorimeter test results reveal that CMS@TETP has better flame retardancy in EP than either CMS or TETP at the same loading level. In comparison with those of pure EP, the mean heat release rate, peak heat release rate, total heat release, and effective heat of combustion of the EP composite containing 3.0 wt% CMS@TETP (EP/CMS@TETP‐3) are respectively reduced by 49.5%, 59.1%, 47.0%, and 46.1%. The glass transition temperatures of EP/CMS@TETP composites are slightly increased than that of pure EP, indicating an increase in the thermal resistance. Thermogravimetric analysis results provide evidence that CMS@TETP has good char‐forming capacity in EP.

Labeling of ethylenediamine tetramethylene phosphonate with 153Sm and 177Lu,Comparison Study

Background 177Lu and 153Sm are perspective radionuclides in terms of applying to nuclear medicine. High-energy beta particles and the relative half-life of the radionuclide are used to achieve an effective palliative treatment of bone metastases. Materials and methods The absorbed doses in different organs and tissues of 177Lu and 153Sm in ionic form and labeled with EDTMP are determined by IDAC-Dose 2.1 (Internal Dose Assessment by Computer) software and WinAct software which used to calculate cumulative activity. 177Lu and 153Sm are lanthanide radionuclide which actively accumulates in liver and bone when used in ionic form. In the case of labeling with EDTMP, the distribution and elimination of the drug occur according to the kinetics of a carrier, EDTMP. The using of osteotropic (Describing any drug etc. that is attracted to, and targets bone) complex allows creating a large dose in the pathological areas and minimizing damages in healthy organs and tissues. Results The effective dose per administered activity is 0.189 mSv/MBq for 177Lu-ionic form, 0.232 mSv/MBq for 153Sm-ionic form and 0.242 mSv/MBq for 177Lu-EDTMP and 0.139 mSv/MBq for 153sm-EDTMP. Conclusion 177Lu and 153Sm labeled with EDTMP are decreasing the liver dose absorption and increasing the bone surface absorption for more effective treatment and minimize side effects.

Phosphorus recovery and leaching of trace elements from incinerated sewage sludge ash (ISSA)

Chemical extraction of phosphorus (P) from incinerated sewage sludge ash (ISSA) is adversely influenced by co-dissolution of metals and metalloids. This study investigated P recovery and leaching of Zn, Cu, Pb, As and Ni from ISSA using inorganic acids (sulphuric acid and nitric acid), organic acids (oxalic acid and citric acid), and chelating agents (ethylenediaminetetraacetic acid (EDTA) and ethylene diamine tetramethylene phosphonate (EDTMP)). The aim of this study was to optimize a leaching process to recover P-leachate with high purity for P fertilizer production. The results show that both organic and inorganic acids extract P-containing phases but organic acids leach more trace elements, particularly Cu, Zn, Pb and As. Sulphuric acid was the most efficient for P recovery and achieved 94% of total extraction under the optimal conditions, which were 2-h reaction with 0.2 mol/L H2SO4 at a liquid-to-solid ratio of 20:1. EDTA extracted only 20% of the available P, but the leachates were contaminated with high levels of trace elements under optimum conditions (3-h reaction with EDTA at 0.02 mol/L, pH 2, and liquid-to-solid ratio of 20:1). Therefore, EDTA was considered an appropriate pre-treatment agent for reducing the total metal/metalloid content in ISSA, which produced negligible changes in the structure of ISSA and reduced contamination during subsequent P extraction using sulphuric acid.

Ethylenediamine tetramethylene phosphonic acid assisted synthesis of palladium nanocubes and their electrocatalysis of formic acid oxidation

The synthesis of Pd nanocrystals of controlled size and morphology has drawn enormous interest due to their catalytic activity. We report a new and efficient strategy for the one-step synthesis of monodispersed Pd nanocubes with ethylenediamine tetramethylene phosphonate (EDTMP) as a complex-forming and capping agent. The morphology, structure, and growth mechanism of the Pd nanocubes were fully characterized via selected area electron diffraction (SAED), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). It was found that the morphology of the Pd nanocrystals in the proposed EDTMP–PdCl2 system could be changed from octahedrons to nanocubes simply by adjusting the amount of iodide used during synthesis. After UV/ozone and electrochemical cleaning, the as-prepared Pd nanocubes demonstrated excellent electrocatalytic activity and stability during formic acid oxidation, owing to their abundant {100} facets and small particle size.

Calculation of the Dose of Samarium-153-Ethylene Diamine Tetramethylene Phosphonate (153Sm-EDTMP) as a Radiopharmaceutical for Pain Relief of bone Metastasis

Introduction One of the important applications of nuclear physics in medicine is the use of radioactive elements as radiopharmaceuticals. Metastatic bone disease is the most common form of malignant bone tumors. Samarium-153-ethylene diamine tetramethylene phosphonate (153Sm-EDTMP) as a radiopharmaceutical is used for pain palliation. This radiopharmaceutical usually emits beta particles, which have a high uptake in bone tissues. The purpose of this study was to calculate the radiation dose distribution of 153Sm-EDTMP in bone and other tissues, using MCNPX Monte Carlo code in the particle transport model. Materials and Methods Dose delivery to the bone was simulated by seeking radiopharmaceuticals on the bone surface. The phantom model had a simple cylindrical geometry and included bone, bone marrow, and soft tissue. Results The simulation results showed that a significant amount of radiation dose was delivered to the bone by the use of this radiopharmaceutical. Conclusion Thebone acted as a fine protective shield against rays for the bone marrow. Therefore, the trivial absorbed dose by the bone marrow caused less damage to bone-making cells. Also, the high absorbed dose of the bone could destroy cancer cells and relieve the pain in the bone.

Optimized production and quality control of (68)Ga-EDTMP for small clinical trials.

Optimized production and quality control of gallium-68 labeled ethylenediamine tetramethylene phosphonate ((68)Ga-EDTMP) as an efficient PET radiotracer for bone scans have been presented. Efforts have been made to present a fast, efficient, cost-effective and facile protocol for (68)Ga-EDTMP productions for clinical trials. (68)Ga-EDTMP was prepared using generator-based (68)GaCl3 and EDTMP at optimized conditions for time, temperature, ligand amount, gallium content followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 155min. (68)Ga-EDTMP was prepared at optimized conditions in 5-10min at 50-60°C (radiochemical purity ≈99±0.88% ITLC, >99% HPLC, specific activity: 15-18GBq/mM). The biodistribution of the tracer demonstrated high bone uptake of the tracer in 10-20min while yielding the best images in 2h. The whole production and quality control of (68)Ga-EDTMP including labeling, purification, HPLC analysis, sterilization and LAL test took 18-20min with significant specific activity for administration to limited number of patients in a PET center.

Samarium-153 EDTMP for metastatic bone pain palliation: The impact of europium impurities

PurposeTo evaluate the impact on the radiation protection policies of the radiocontaminants in Samarium-153 ethylenediamine tetramethylene phosphonate (153Sm-EDTMP). MethodsThe internal contamination of patients treated with 153Sm-EDMTP for palliation of painful disseminated multiple bone metastases due to long-lived impurities was assessed by direct measurements. These measurements were coupled with dose-rate measurements close to their bodies and spectroscopic analysis of the residual activity in post-treatment radiopharmaceutical vials. ResultsWhole-body counting carried out in six patients showed a 30–81-kBq europium −152 plus europium-154 contamination. The 0.85 mean 152Eu- to -154Eu activity ratio obtained by direct counting was similar to that assessed by analysis of post-treatment residual activities in twelve radiopharmaceutical vials following radiopharmaceutical injection. ConclusionsThe long-lived radiocontaminants in the patient's bodies and the treatment wastes require modifications of the applicable radiation protection policies.

Modeling the time dependent biodistribution of Samarium-153 ethylenediamine tetramethylene phosphonate using compartmental analysis

AimThe main purpose of this work was to develop a pharmacokinetic model for the bone pain palliation agent Samarium-153 ethylenediamine tetramethylene phosphonate ([153Sm]-EDTMP) in normal rats to analyze the behavior of the complex. BackgroundThe use of compartmental analysis allows a mathematical separation of tissues and organs to determine the concentration of activity in each fraction of interest. Biodistribution studies are expensive and difficult to carry out in humans, but such data can be obtained easily in rodents. Materials and methodsWe have developed a physiologically based pharmacokinetic model for scaling up activity concentration in each organ versus time. The mathematical model uses physiological parameters including organ volumes, blood flow rates, and vascular permabilities; the compartments (organs) are connected anatomically. This allows the use of scale-up techniques to predict new complex distribution in humans in each organ. ResultsThe concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of 153Sm-EDTMP was modeled and drawn as a function of time. ConclusionsThe variation of pharmaceutical concentration in all organs is described with summation of 6–10 exponential terms and it approximates our experimental data with precision better than 2%.

Palliative treatment of bone metastases with samarium-153 EDTMP at onset of pain

We evaluated the pain response and daily discomfort in patients suffering from a borderline degree of bone pain due to breast or lung cancer bone metastases, who had undergone early palliative radionuclide treatment. The results were compared with those from patients who had received standard analgesic therapy. Twenty-one patients (65.7 ± 3 years; 17 women) with metastatic bone cancer underwent samarium-153 (Sm-153) ethylene diamine tetramethylene phosphonate (EDTMP) administration (group A) and 18 patients (64.3 ± 8 years; 16 women)continued to receive standard analgesics (group B; control group). The patients kept a daily pain diary assessing both their discomfort and the pain at specific sites by means of a visual analog scale, rating from 0 (no discomfort–no pain)to 10 (worst discomfort–pain). These diaries were reviewed weekly for 2 months and three physicians rated the pain response on a scale from -2 (considerable deterioration) to +2 (considerable improvement). Baseline characteristics were similar in both groups. The reduction of total discomfort and of bone pain in group A was significantly greater compared to group B (p < 0.0001). A significant improvement of clinical conditions was observed in group A, where the physician rate changed from -1 to 1, compared to group B in which the rate changed from -1 to 0. Sm-153 EDTMP therapy can be considered for patients with bone pain from breast and lung cancer in advance, i.e.,before the establishment of severe pain syndrome.

English

Samarium-153-ethylene diamine tetramethylene phosphonate (samarium-153 EDTMP) is a novel systemic radiopharmaceutical, used for treatment of bone pain due to metastatic disease. We report a patient with carcinoma prostate, diffuse metastatic bone disease with severe back pain that was refractory to analgesics and morphine. He was also found to be anaemic (haemoglobin 8.1 g/dL). Inspite of anaemia and diffuse metastatic bone disease being relative contraindications for the use samarium-153-EDTMP, because of its potential for causing radiation induced myelotoxicity, the patient was treated with this modality and showed a remarkable response in pain control within a few days. He developed mild radiation induced myelotoxicity, which was subsequently managed with blood transfusion and supportive care. The present case highlights the utility of samarium-153 EDTMP therapy in patients with intractable pain due to diffuse metastatic bone disease.

Samarium-153-ethylene diamine tetramethylene phosphonate, a beta-emitting bone-targeted radiopharmaceutical, useful for patients with osteoblastic bone metastases

Bone metastases are prevalent among cancer patients and frequently cause significant morbidity. Oncology providers must mitigate complications associated with bone metastases while limiting therapy-related adverse effects and their impact on quality of life. Multiple treatment modalities, including chemotherapy, surgery, external beam radiation therapy, and radioisotopes, among others, have been recommended and utilized for palliative treatment of bone metastases. Radioisotopes such as samarium-153 are commonly used in the setting of multifocal bone metastases due to their systemic distribution, affinity for osteoblastic lesions, acceptable toxicity profile, and convenience of administration. This review focuses on samarium-153, first defining its radiobiologic and pharmacokinetic properties before describing many clinical trials that support its use as a safe and effective tool in the palliation of patients with bone metastases.

Repetitively dosed docetaxel and 153samarium‐EDTMP as an antitumor strategy for metastatic castration‐resistant prostate cancer

β-emitting bone-seeking radiopharmaceuticals have historically been administered for pain palliation whereas docetaxel prolongs life in patients with metastatic castration-resistant prostate cancer (mCRPC). In combination, these agents simultaneously target the bone stroma and cancer cell to optimize antitumor effects. The toxicity and efficacy when each agent is combined at full, recommended doses, in a repetitive fashion is not well established. Patients with progressive mCRPC and ≥ 3 bone lesions received (153) Sm-EDTMP (samarium-153 ethylene diamine tetramethylene phosphonate) at a dose of 1.0 mCi/kg every 9 weeks and docetaxel at a dose of 75 mg/m(2) every 3 weeks. In the absence of unacceptable toxicity, patients were allowed to continue additional cycles, defined by 9 weeks of treatment, until intolerance or biochemical/radiographic disease progression. Of the 30 patients treated, approximately 50% were considered to be taxane-naive, 36.7% were taxane-refractory, and 13.3% had previously been exposed to taxanes but were not considered refractory. Patients received on average 2.5 cycles of treatment (6.5 doses of docetaxel and 2.5 doses of (153) Sm-EDTMP). Twelve patients (40%) demonstrated a decline in their prostate-specific antigen level of ≥ 50%. The median progression-free survival (biochemical or radiographic) was 7.0 months and the overall survival was 14.3 months. Nine patients (30%) did not recover platelet counts >100 K/mm(3) after a median of 3 cycles to allow for additional treatment, with 4 patients experiencing prolonged thrombocytopenia. The most common reasons for trial discontinuation were progressive disease and hematologic toxicity. The results of the current study indicate that (153) Sm-EDTMP can be safely combined with docetaxel at full doses on an ongoing basis in patients with mCRPC. Although thrombocytopenia limited therapy for some patients, preliminary efficacy supports the strategy of combining a radiopharmaceutical with chemotherapy, which is an appealing strategy given the anticipated availability of α emitters that can prolong survival.

Samarium-153-ethylene diamine tetramethylene phosphonate (EDTMP) therapy in the management of refractory bone pain in a patient with carcinoma prostate and diffuse bone metastasis

Samarium-153-ethylene diamine tetramethylene phosphonate (EDTMP) therapy in the management of refractory bone pain in a patient with carcinoma prostate and diffuse bone metastasis

Bone-Targeting Radiopharmaceuticals Including Radium-223

Bone-seeking radionuclides including samarium-153 ethylene diamine tetramethylene phosphonate and strontium-89 have been used for decades in the palliation of pain from bone metastases especially from prostate cancer. Emerging evidence of improved survival in metastatic castration-resistant prostate cancer (CRPC) with the first-in-class α-radionuclide, radium-223 (Ra) has rekindled interest in the role of bone-seeking radionuclide therapy.We review the literature for randomized controlled trials of bone-seeking radionuclides and explore some of the issues regarding the optimal use of these agents. In particular, we discuss dose, dose rate, radiobiology, and quality of radiation and postulate on potential future directions in particular combination schedules. β-Emitting, bone-seeking radionuclides have proven ability to control pain in prostate cancer metastatic to bone with pain response rates in the order of 60% to 70% when used as single agents. Most of the published trials were underpowered to detect differences in survival; however, there is evidence of the potential for disease modification when these agents are used in combination with chemotherapy or in multiple cycles.Data from the recent phase III ALSYMPCA trial that compared Ra to placebo in symptomatic CRPC demonstrate a significant improvement in median overall survival of 3.6 months for patients with symptomatic CRPC metastatic to bone treated with 6 cycles of the α-emitting radionuclide Ra compared with placebo. The success of Ra in improving survival in CRPC will lead this agent to become part of the treatment paradigm for this disease, and with such an excellent safety profile, Ra has huge potential in combination strategies as well as for use earlier in the natural history of metastatic prostate cancer.

Incidental finding of hiatal hernia on 99mTc-Sestamibi whole-body scan in thyroid cancer evaluation

We investigated the safety and feasibility of the combination of samarium-153-ethylenediamine tetramethylene phosphonate (153Sm-EDTMP)-incorporated bone cement (BC) with percutaneous vertebroplasty (PVP) in dogs.153Sm-EDTMP-incorporated BC was prepared by combining solid 153Sm-EDTMP and polymethylmethacrylate (PMMA) immediately before PVP. It was then injected into the vertebrae of four healthy mongrel dogs (two males and two females) by PVP under CT guidance. Each dog was subjected to five PVP sessions at a 153Sm-EDTMP dose of 30–70 mCi. The suppressive effect of local injection of 153Sm-EDTMP on the hematopoietic system was evaluated through counting of peripheral blood cells. Distribution of 153Sm-EDTMP-incorporated BC and the status of tissues adjacent to injected vertebrae were evaluated with SPECT, CT and MRI. Histopathology was carried out to assess the influence of PVP on the vertebra and adjacent tissues at the microscopic level.PVP was done successfully, and all dogs exhibited normal behavior and stable physical signs after procedures. 153Sm-EDTMP-incorporated BC was concentrated mainly in target vertebrae, and the peripheral blood cells remained within normal range. The spinal cord and tissues around BC did not exhibit signs of injury even when the dosage of 153Sm-EDTMP increased from 30 mCi to 70 mCi.A dose lower than 70 mCi of 153Sm is safe when it was injected into vertebrae. 153Sm-EDTMP-incorporated BC did not influence the effect of PVP. This means might strengthen anti-tumor activity locally for vertebra with osseous metastasis without damaging adjacent tissues.