Aminophosphonates, like glyphosate (GS) or metal chelators such as ethylenediaminetetra(methylenephosphonic acid) (EDTMP), are released on a large scale worldwide. Here, we have characterized a bacterial strain capable of degrading synthetic aminophosphonates. The strain was isolated from LC/MS standard solution. Genome sequencing indicated that the strain belongs to the genus Ochrobactrum. Whole-genome classification using pyANI software to compute a pairwise ANI and other metrics between Brucella assemblies and Ochrobactrum contigs revealed that the bacterial strain is designated as Ochrobactrum sp. BTU1. Degradation batch tests with Ochrobactrum sp. BTU1 and the selected aminophosphonates GS, EDTMP, aminomethylphosphonic acid (AMPA), iminodi(methylene-phosphonic) (IDMP) and ethylaminobis(methylenephosphonic) acid (EABMP) showed that the strain can use all phosphonates as sole phosphorus source during phosphorus starvation. The highest growth rate was achieved with AMPA, while EDTMP and GS were least supportive for growth. Proteome analysis revealed that GS degradation is promoted by C-P lyase via the sarcosine pathway, i.e., initial cleavage at the C-P bond. We also identified C-P lyase to be responsible for degradation of EDTMP, EABMP, IDMP and AMPA. However, the identification of the metabolite ethylenediaminetri(methylenephosphonic acid) via LC/MS analysis in the test medium during EDTMP degradation indicates a different initial cleavage step as compared to GS. For EDTMP, it is evident that the initial cleavage occurs at the C-N bond. The detection of different key enzymes at regulated levels, form the bacterial proteoms during EDTMP exposure, further supports this finding. This study illustrates that widely used and structurally more complex aminophosphonates can be degraded by Ochrobactrum sp. BTU1 via the well-known degradation pathways but with different initial cleavage strategy compared to GS.

Determination of biodegradation of synthetic phosphonates such as aminotris(methylenephosphonic acid) (ATMP), ethylenediamine tetra(methylenephosphonic acid) (EDTMP), or diethylenetriamine penta(methylenephosphonic acid) (DTPMP) is a great challenge. Commonly, ready biodegradability of organic substances is assessed by OECD 301 standard tests. However, due to the chemical imbalance of carbon to phosphorus synthetic phosphonates do not promote microbial growth and, thus, limiting its biodegradation. Therefore, standard OECD test methods are not always reliable to predict the real biodegradability of phosphonates. In the presented study, we report the development of a standardized batch system suitable to synthetic phosphonates such as ATMP, EDTMP, DTPMP and others. The novel standard batch test is applicable with pure strains, activated sludge from different wastewater treatment plants (i.e., municipal and industrial), and with tap water as inoculum. We optimized the required calcium and magnesium exposure levels as well as the amount of the start inoculum biomass. We demonstrated that our test also allows to determine several parameters including ortho-phosphate (o-PO43-), total phosphorus (TP), ammonium (NH4+) and total organic carbon (TOC). In addition, also LC/MS analyses of cell-free medium is applicable for determining the mother compounds and metabolites. We applied our optimized standardized batch with selected phosphonates and evidenced that the chemical structure has a major influence of the microbial growth rates. Thus, our novel batch test overcomes drawbacks of the OECD 301 test series for determination of easy biodegradability for stoichiometric imbalanced organic compounds such as phosphonates.

BACKGROUND: With its suitable nuclear decay characteristics and large-scale production feasibility with adequate specific activity, 177Lu is regarded as an excellent radionuclide for developing bone pain palliation agent. Ethylenediamine-tetramethylene phosphonic acid (EDTMP) is a preferred carrier molecule for radiolanthanides, such as 177Lu. The present paper describes the synthesis of EDTMP and the development of a ready-to-use kit for the preparation of 177Lu-EDTMP and its quality control in accordance with the quality and safety criteria required for medicinal use.
METHODS: EDTMP was synthesized by a modified Mannich-type reaction, and the structure was characterized using NMR and IR spectroscopy. Optimization of radiolabeling conditions was done with two different salt forms of EDTMP. The labeling yield was checked by paper chromatography with radiation detection. Kit was developed as a lyophilized mixture of EDTMP and sodium bicarbonate in a maximum volume of 5 mL. Labeling efficiency, radionuclidic purity, radiochemical purity, sterility, and pyrogenicity analysis were performed as the quality control of the labeled kit.
RESULTS: The analytical data for the structure determination and purity of the synthesized ligand were in agreement with authentic commercial samples used in radiopharmacy.177Lu-EDTMP complex was prepared using synthesized EDTMP ligand under optimized labeling conditions with high labelling yield (>99%). The radiolabeling yields of the EDTMP kit at room temperature after 30 min and 48 hours were 99.46% and 99.00%.
CONCLUSIONS: The developed EDTMP kit enables an instant one-step preparation of the radiopharmaceutical of high radiochemical purity (>99%) and has a sufficiently long shelf life. This enables the routine production of the 177Lu-EDTMP in nuclear medicine clinics without requiring experienced staff.

BACKGROUND: Synthesis of 225Actinium derivatives using PSMA-617, DOTATATE peptides and EDTMP ligand was afforded. Detailed experimental, quality control (QC) and stability studies were well described. The radiolabelling reactions were performed in mild conditions with desirable radiochemical yields and high radiochemical purities.
METHODS: PSMA-617, and DOTATATE were radiolabelled with 225Actinium in 0.1 M HCl in the presence of ascorbate buffer solution and passed through the C-18 light cartridge for purification and the product was eluted by ethanol-water solution. EDTMP was also radiolabelled with 225Actinium without using any stabilizer and purification step. All products were well analyzed by R-TLC and R-HPLC. The stability of those compounds was also studied within the valid time.
RESULTS: 225Ac-DOTATATE and 225Ac-PSMA-617 were obtained at the same condition. The radiochemical yield of 225Ac-DOTATATE was less than 225Ac-PSMA 617. Stability experiments indicated decay daughters of 225Actinium appeared after T0 +1 h due to the recoil effect radiolysis. On the other hand, 225Ac-EDTMP was more stable than DOTA-peptide radiolabelled compounds. 225Ac-EDTMP was produced with more than 95% radiochemical yield and 99% radiochemical purity.
CONCLUSIONS: A detailed chemistry study was presented for the synthesis of 225Actinium derivatives in mild conditions with absolute radiochemical purities and high yields. Experimental results showed that 225Ac-EDTMP could be a suitable alternative radiopharmaceutical for bone metastases arising from primer tumors as a cocktail therapy.

Soil washing is a rapid and efficient remediation technique for soil contaminated by heavy metals. In this study, Cd, Pb, and Zn were removed from contaminated soil by ethylenediamine tetra (methylene phosphonic acid) (EDTMP) and polyacrylic acid (PAA). We then investigated the effect of varying the concentration, pH and duration of the washing processes. Single-factor experiments suggest that the PAA washing process may be dominated by electrostatic adsorption, and is suitable for remediation under weak acid and neutral conditions. Meanwhile, EDTMP remediation might be dominated by chelation, which is favorable in strong acid and alkaline environments. In a quadratic saturation D-optimization design (QSDD), we optimized the washing parameters and further explored the washing mechanism including primary factor, principal effect, interaction effect, and the optimal washing conditions, with simultaneously changing multiple influencing factors. The optimum efficiencies of Cd, Pb, and Zn removal were 92.74%, 96.14%, and 50.76% respectively in EDTMP remediation, and 84.62, 79.24, and 41.66% respectively in PAA remediation. The washing processes effectively reduced the availability of Cd, Pb, and Zn in contaminated soil, without noticeably affecting soil chemical properties. Therefore, the washing incurred little ecological risk. EDTMP and PAA are suitable remediation agents of soil contaminated by heavy metals.

Over the past few decades, several bone-seeking radiopharmaceuticals including various bisphosphonate ligands and β-emitting radionuclides have been developed for bone pain palliation. Recently, (177)Lu was successfully labeled with zoledronic acid ((177)Lu-ZLD) as a new generation potential bisphosphonate and demonstrated significant accumulation in bone tissue. In this work, the absorbed dose to each organ of human for (177)Lu-ZLD and (177)Lu-ethylenediaminetetramethylene phosphonic acid ((177)Lu-EDTMP;as the only clinically bone pain palliation agent) was investigated based on biodistribution data in rats by medical internal radiation dosimetry (MIRD) method. (177)Lu-ZLD and (177)Lu-EDTMP were prepared in high radiochemical purity (>99%, instant thin layer chromatography (ITLC)) at the optimized condition. The biodistribution of the complexes demonstrated fast blood clearance and major accumulation in the bone tissue. The highest absorbed dose for both (177)Lu-ZLD and (177)Lu-EDTMP is observed in trabecular bone surface with 12.173 and 10.019 mSv/MBq, respectively. The results showed that (177)Lu-ZLD has better characteristics compared to (177)Lu-EDTMP and can be a good candidate for bone pain palliation.

In this work, the absorbed dose of human organs for (177)Lu-BPAMD was evaluated based on biodistribution studies into the Syrian mice by RADAR method and was compared with (177)Lu-EDTMP as the only clinically used Lu-177 bone-seeking agent. The highest absorbed dose for both (177)Lu-BPAMD and (177)Lu-EDTMP is observed on the bone surface with 8.007 and 4.802 mSv/MBq. Generally, (177)Lu-BPAMD has considerable characteristics compared with (177)Lu-EDTMP and can be considered as a promising agent for the bone pain palliation therapy.

BACKGROUND: Particle-emitting, bone-seeking radiopharmaceuticals have attracted the attention of the nuclear medicine community over the last three decades for the treatment of the pain of osteoblastic metastases. The objectives of this research were to produce quality-controlled (159)Gd-EDTMP in order to provide a new therapeutic radiopharmaceutical for use in clinical applications.
METHODS: The investigation was an experimental study in which (159)Gd (T1/2=18.479 h, Eβ (max)=970.60 keV, Eγ=363.55 (11.4%) keV] was produced by thermal neutron bombardment of natural Gd2O3 at the Tehran Research Reactor (TRR) for a period of 7 d at a flux of 3-4×10(13) neutrons/cm(2).s. It was then quality-controlled and used to radio-label the in-house prepared ethylene diamine tetra acetic acid (EDTM).
RESULTS: Complexation parameters were optimized to achieve maximum yields (>99%). The radiochemical purity of (159)Gd-EDTMP was checked by radio thin layer chromatography RTLC. It was found to retain its stability at room temperature (>95%). Bio-distribution studies of the complexes conducted in wild rats showed significant bone uptake with rapid clearance from blood.
CONCLUSIONS: The properties of the (159)Gd-EDTMP that was produced suggest then use of a new, efficient, palliative therapeutic agent for metastatic bone pain instead of some other current radiopharmaceuticals.

OBJECTIVE: The objective of the present work was to develop a freeze-dried ethylenediaminetetramethylene phosphonic acid (EDTMP) kit, suitable for the convenient and single-step preparation of (177)Lu-EDTMP, which is currently being evaluated as a promising radiopharmaceutical for providing palliative care to patients suffering from skeletal metastases and to assess the potential of the agent in human patients.
METHODS: Lyophilized EDTMP kits having identical composition with Quadramet(®) were prepared using EDTMP, NaOH, and anhydrous CaCO3. The (177)Lu-EDTMP patient dose was prepared by incubating the kit materials dissolved in 1 mL of water for injection and (177)LuCl3, produced in-house, at room temperature for 15 minutes. Pharmacokinetic behavior of the agent was studied by carrying out biodistribution and scintigraphic imaging studies in normal Wistar rats. Clinical studies were performed by administering the preparation in patients suffering from disseminated skeletal metastases.
RESULTS: Five batches of freeze-dried EDTMP kits with 50 kit vials in each batch were prepared. Each kit vial comprised a lyophilized mixture of 35 mg EDTMP, 14.1 mg NaOH, and 5.8 mg of CaCO3. The (177)Lu-EDTMP complex was prepared with excellent radiochemical purity (>99%) and high stability (>98% until 9 days postpreparation) using these kits. Radiochemical studies showed that this kit could be used within a pH range of 6-9 and with (177)Lu having specific activity as low as 925 GBq · g(-1) (25 Ci · g(-1)) for the preparation of up to 3.7 GBq (100 mCi) of (177)Lu-EDTMP. Biodistribution studies in animals revealed selective accumulation of the agent in skeleton (∼ 60% of the injected activity) with major renal clearance. Preliminary clinical studies in 10 patients exhibited selective accumulation of the radiotracer in skeletal lesions and provided significant pain relief thereby improving the quality of life of the patients.
CONCLUSIONS: Freeze-dried EDTMP kits, suitable for the preparation of patient doses of (177)Lu-EDTMP, have been developed and used in preliminary studies for treating the cancer patients with disseminated skeletal metastases. The kit may also find use for the preparation of other potential bone pain palliation agents, such as (153)Sm-EDTMP.

Open tubular (OT) capillary columns have been increasingly used in a variety of fields of separation science such as CEC, LC, and SPE. Especially their application in CEC has attracted a lot of attention for their outstanding separation performance. Various forms of OT stationary phase materials have been employed such as in-situ prepared polymers, molecular imprinted polymers (MIPs), brush ligands, host ligands, block copolymers, aptamers, carbon nanotubes, polysaccharides, proteins, tentacles, nanoparticles, monoliths, and polyelectrolyte multi-layers. They have been prepared either in the chemically bound format or physically adsorbed format. Sol-gel technologies and nanoparticles have been sometimes involved in their preparation. There have been also some unique miscellaneous studies, for example, adopting preferentially adsorbed mobile phase components as stationary phases. In this review, recent progresses since mostly 2007 will be critically discussed in detail with some summarized descriptions for the work before the date.