Optimal production and purification of n.c.a.143Pr as a promising palliative agent for the treatment of metastatic bone pain.

This study proposes the beta-emitting radioisotope 143Pr as a promising candidate for palliative treatment of metastatic bone pain due to its desirable physical decay characteristics. An optimized process was developed for the production and purification of non-carrier-added 143Pr using a medium flux research reactor. Calculations were performed to determine the optimal irradiation time and cooling period for irradiating 1 mg of natural cerium oxide to indirectly produce 143Pr through the decay of 143Ce. Following irradiation and cooling, extraction chromatography was employed to efficiently isolate 143Pr from the irradiated target material. A column containing Ln-resin was used along with nitric acid as the mobile phase and an optional oxidation step with NaBrO3/ascorbic acid to separate 143Pr from impurities such as 143Ce and 141Ce. Radionuclidic purity of over 99.995% was achieved as confirmed through gamma spectroscopy, demonstrating effective separation of 143Pr. Additional quality control analyses established the chemical and radiochemical purity of the purified 143Pr nitrate product. With a half-life of 13.6 days and maximum beta energy of 0.937 MeV, 143Pr exhibits favorable properties for palliative bone pain therapy. This study therefore provides a viable method for producing high-purity 143Pr through the optimized irradiation and purification processes described. Further investigation is warranted to explore potential clinical applications of 143Pr for palliation of metastatic bone cancer pain.

Strongly Anchoring Polysulfides by Hierarchical Fe3O4/C3N4 Nanostructures for Advanced Lithium-Sulfur Batteries.

Li-S batteries have attracted considerable interest as next-generation energy storage devices owing to high energy density and the natural abundance of sulfur. However, the practical applications of Li-S batteries are hampered by the shuttle effect of soluble lithium polysulfides (LPS), which results in low cycle stability. Herein, a functional interlayer has been developed to efficiently regulate the LPS and enhance the sulfur utilization using hierarchical nanostructure of C3N4 (t-C3N4) embedded with Fe3O4 nanospheres. t-C3N4 exhibits high surface area and strong anchoring of LPS, and the Fe3O4/t-C3N4 accelerates the anchoring of LPS and improves the electronic pathways. The combination of these materials leads to remarkable battery performance with 400% improvement in a specific capacity and a low capacity decay per cycle of 0.02% at 2 C over 1000 cycles, and stable cycling at 6.4 mg cm-2 for high-sulfur-loading cathode.

Highly Stable 177Lu-Organic Framework as a Potential Agent for Treatment of Metastatic Bone.

In this paper, the metal organic framework (MOF) concept is contributed to rearrange the bone-seeking agent composed of carrier-free lutetium-177 (Lu-177), 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraaminomethylenephosphonate (DOTMP) and cupper (II) (Cu (II)) for preparation of a potential agent for treatment of bone metastases. The product was characterized (infra-red spectroscopy, IR, and X-ray diffraction analysis) and quality-controlled (radio-thin layer chromatography, (RTLC)). The stability and in vitro hydroxyapatite binding was checked up to 1.5 month at 37 °C in human serum. Radio-MOF crystals and radio-MOF particles that were obtained by varying the synthesizing conditions (including pH and temperature) showed similar IR patterns and similar elemental analysis results. The final product was synthesized at pH = 8, stirring at room temperature (yield >99%, RTLC, particle size: 90 ± 20 nm). Biodistribution study experiments showed interesting bone-seeking (%ID/g: 8.5%) affinity of the prepared formula with no significant liver or lung uptake. Also high accumulation of radio-complex in bone tissue was estimated by the modeling of the radiation dose delivery using radiation dose assessment resource software. This novel radio-MOF with promising therapeutic results is the first study of the usage of the MOF concept to provide a high payload of Lu-177 for treatment of bone metastases. As it was expected, the most important outcome of the paper was higher bone-uptake rates rather than conventional 177Lu-DOTMP.

Feasibility study for production and quality control of Yb-175 as a byproduct of no carrier added Lu-177 preparation for radiolabeling of DOTMP.

Skeletal uptake of ß- emitters of DOTMP complexes is used for the bone pain palliation. In this study, two moderate energy ß- emitters, 177Lu (T1/2 = 6.7 days, Eßmax = 497 keV) and 175Yb (T1/2 = 4.2 days, Eßmax = 480 keV), are considered as potential agents for the development of the bone-seeking radiopharmaceuticals. Since the specific activity of the radiolabelled carrier molecules should be high, the non-carrier-added (NCA) radionuclides have an effective role in nuclear medicine. Many researchers have presented the synthesis of NCA 177Lu. Among these separation techniques, extraction chromatography has been considered more capable than other methods. In this study, a new approach, in addition to production of NCA 177Lu by EXC procedure is using pure 175Yb that was usually considered as a waste material in this method but because of high radionuclidic purity of 175Yb produced by this method we used it for radiolabeling as well as NCA 177Lu. To obtain optimum conditions, some effective factors on separation of Lu/Yb by EXC were investigated. The NCA 177Lu and pure 175Yb were produced with radionuclidic purity of 99.99 and 99.97% respectively by irradiation of enriched 176Yb target in thermal neutron flux of 5 × 1013 n/cm2 s for 14 days. 177Lu-DOTMP and 175Yb-DOTMP were obtained with high radiochemical purities (> 95%) under optimized reaction conditions. Two radiolabeled complexes exhibited excellent stability at room temperature. Biodistribution studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation of activity in other non-target organs for two radiolabelled complexes.

Production, quality control, and determination of human absorbed dose of no carrier added 177 Lu-risedronate for bone pain palliation therapy.

In this study, the radiocomplexation of risedronic acid, a potent bisphosphonate with a no carrier added (NCA) 177 Lu, was investigated and followed by quality control studies, biodistribution evaluation, and dosimetry study for human based on biodistribution data in Wistar rats. The moderate energy ß- emitter, 177 Lu (T½  = 6.7 days, Eßmax  = 497 keV), has been considered as a potential agent for development of bone-seeking radiopharmaceuticals. Because the specific activity of the radiolabeled carrier molecules should be high, the NCA radionuclides have an effective role in nuclear medicine. Many researchers illustrated an NCA 177 Lu production; among these separation techniques, extraction chromatography has been considered more capable than other methods. The NCA 177 Lu was produced with specific activity of 48 Ci/mg and radionuclidic purity of 99.99% by the irradiation of enriched 176 Yb target in thermal neutron flux of 4 × 1013  n·cm-2 ·s-1 for 14 days. The NCA 177 Lu was mixed to a desired amount of sodium risedronate (15 mg/mL, 200 µL) and incubated with stirring at 95°C for 30 minutes. The radiochemical purity of 177 Lu-risedronate was determined by radio thin-layer chromatography, and high radiochemical purities (>97%) were obtained under optimized reaction conditions. The complex was injected to Wistar rats, and complex biodistribution was performed 4 hours to 7 days postinjections showing high bone uptake (9.8% ± 0.24% ID/g at 48 hours postinjection). Also, modeling the radiation dose delivery by RADAR software for the absorbed dose evaluation of each human organ showed a major accumulation of the radiocomplex in bone tissue.

Production and quality control 177Lu (NCA)-DOTMP as a potential agent for bone pain palliation.

Skeletal uptake of radiolabeled-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetramethylene phosphoric acid (e.g., 177Lu-DOTMP) complex, is used for bone pain palliation. The moderate energy of ß-emitting 177Lu (T½ = 6.7 d, Eßmax = 497keV) has been considered as a potential radionuclide for development of the bone-seeking radiopharmaceutical. Since the specific activity of the radiolabeled carrier molecules should be high, the "no-carrier-added radionuclides" have sig-nificant roles in nuclear medicine. Many researchers illustrated no-carrier-added 177Lu production; among these separation techniques such as ion exchange chromatography, reversed phase ion-pair, and electrochemical method, extraction chromatography has been considered more capable than other methods. In order to optimize the conditions, some effective factors on separation of Lu/Yb were investigated by EXC. The NCA 177Lu, produced by this method, was mixed with 300 µl of DOTMP solution (20 mg in 1 mL of 0.5 M NaHCO3, pH = 8) and incu-bated under stirring at room temperature for 45 min. Radiochemical purity of the 177Lu-DOTMP complex was determined using radio-thin-layer chromatography (RTLC) method. The complex was injected to wild-type rats and biodistribution was then studied for seven days. The NCA 177Lu was produced with specific activ-ity of 48 Ci/mg and with a radinuclidic purity of 99.99% through irradiation of enriched 176Yb target (1 mg) in a thermal neutron flux of 4 × 1013 n.cm-2.s-1 for 14 days. 177Lu-DOTMP was obtained with high radiochemical purities (> 98%) under optimized reaction conditions. The radiolabeled complex exhibited excellent stability at room temperature. Biodistribution of the radiolabeled complex studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation within the other nontargeted organs.

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

AIM: The main purpose of this work was to develop a pharmacokinetic model for the bone pain palliation agent Samarium-153 ethylenediamine tetramethylene phosphonate ([(153)Sm]-EDTMP) in normal rats to analyze the behavior of the complex. BACKGROUND: The 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 METHODS: We 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. RESULTS: The concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of (153)Sm-EDTMP was modeled and drawn as a function of time. CONCLUSIONS: The 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%.

Thermoluminescent and Monte Carlo dosimetry of a new 170Tm brachytherapy source.

In this Study characteristics of a new 170Tm brachytherapy seed using thermoluminescent dosimeter and also the Monte Carlo simulations to evaluate between calculated and measured values was determined. Titanium tube contained Tm(NO3)3 powders bombardment at the Tehran Research Reactor (TRR) for a period of 7 days at a flux of 2-3 × 10(13) neutrons/cm2 s. To obtain the radial dose function, g(r), and the anisotropy function, F(r, θ), according to the AAPM TG-43U1 recommendations, 30 cm × 30 cm × 15 cm phantoms of Perspex slabs were used. Brachytherapy dose distributions were simulated with the MCNP5 Monte Carlo (MC) radiation transport code. The MCPLIB04 photon cross-section library was applied using data from ENDF/B-VI. Cell-heating tally, F6 was employed to calculate absorbed dose in two separate runs for both beta and gamma particles. The calculated dose rate constant for the HDR source was found to be 1.113 ± 0.021 cGyU(-1) h(-1). Nominal uncertainty in the measured and calculated radial dose functions, g(r), for the IR-(170)Tm source in Perspex is tabulated is approximately 6% (ranging from 2% to 9%). The anisotropy function, F(r, θ), of the IR-(170)Tm source was measured at radial distances of r = 1.5, 2, 3, 5 cm relative to the seed center, and polar angles θ ranging from 0° to 330° in 30° increments.

Optimization of 90 Y-antiCD20 preparation for radioimmunotherapy.

CONTEXT: The advent of monoclonal antibodies such as Rituximab, in recent years, has brought about decisive progress in the treatment of aggressive and indolent non-Hodgkin's lymphoma. AIMS: A further tried and tested improvement to the unmodified antibody has been its coupling to the beta-emitters Y-90. The optimization of 90 Y-antiCD20 radioimmunoconjugate production and quality control methods for future clinical studies in the country was targeted in this work. MATERIALS AND METHODS: The antibody was labeled with 90 Y-yttrium chloride (185 MBq) after conjugation with freshly prepared ccDTPA. Y-90 chloride was obtained by thermal neutron flux (4 × 10 13 n/cm 2 /s) of a natural Y 2 O 3 sample, dissolved in acidic media. Radiolabeling was completed in 24 h by the addition of DTPA-Rituximab conjugate at room temperature. STATISTICAL ANALYSIS USED: All values were expressed as mean ± standard deviation (mean ± SD), and the data were compared using Student's t-test. Statistical significance was defined as P < 0.05. RESULTS: Radiochemical purity of 96% was obtained by using ITLC method for the final radioimmunoconjugate (specific activity = 440-480 MBq/mg). The final isotonic 90 Y-Rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies in normal rats were carried out to determine the radioimmunoconjugate distribution up to 72 h. CONCLUSION: The results showed that 90 Y-DTPA-Rituximab could be considered for further evaluation in animals and possibly in humans as a radiopharmaceutical for use in radioimmunotherapy against non-Hodgkin's lymphomas. Because of the importance of developing anti-lymphoma B agents in nuclear medicine for country use, an optimized radiolabeling method has been introduced.

Production, Quality Control and Pharmacokinetic Studies of (177)Lu-EDTMP for Human Bone Pain Palliation Therapy Trials.

Developing new bone pain palliation agents is a mandate in handling end-stage cancer patients around the world. Possibly, Lu-177 ethylenediaminetetramethylene phosphonic acid ((177)Lu-EDTMP) is a therapeutic agent which can be widely used in bone palliation therapy. In this study, (177)Lu-EDTMP complex was prepared successfully using synthesized EDTMP ligand and (177)LuCl3. Lu-177 chloride was obtained by thermal neutron irradiation (4 × 10(13) n.cm(-2)s(-1)) of natural Lu2O3 samples. Radiochemical purity of (177)Lu-EDTMP was determined by ITLC (more than 99%). Stability studies of the final preparations in the presence of human serum were performed. The biodistribution of (177)Lu-EDTMP and (177)LuCl3 in wild-type rats was studied by SPECT imaging. A comparative accumulation study for (177)Lu-EDTMP and (177)LuCl3 was performed for vital organs up to 7 days. The complex was obtained in high radiochemical purity (more than 99%). The complex was stable in vitro in presence of human serum as well as final formulation. Significant bone uptake (> 70%) was observed for the radiopharmaceutical. Due to better physical properties of Lu-177 compared to Sm-153 and acceptable biodistribution results of the compound, (177)Lu-EDTMP seemed to be an interesting new candidate for clinical trials for bone pain palliation therapy.

Production, quality control and pharmacokinetic studies of Ho-EDTMP for therapeutic applications.

(166)Ho-EDTMP is a major therapeutic agent which is widely used in bone palliation therapy. In this study, a (166)Ho-EDTMP complex was prepared successfully using an in-house synthesized EDTMP ligand and (166)HoCl(3). Ho-166 chloride was obtained by thermal neutron irradiation (1 Ã 10(13) ncm(â2)s(â1)) of natural Ho(NO(3))(3) samples (specific activity = 3â5 GBq/mg), dissolved in acidic media. The radiochemical purity of (166)Ho-EDTMP was checked by ITLC (>99%) and stability studies in presence of human serum and final preparation were performed. The biodistribution of (166)Ho-EDTMP and (166)HoCl(3) in wild-type rats was checked by scarification. SPECT imaging of (166)Ho-EDTMP was also performed in wild-type rats. A comparative accumulation study for (166)Ho-EDTMP and (166)HoCl(3) was performed for vital organs up to 48h. Significant bone accumulation (>70%) of the tracer in 48h was observed.

Synthesis and characterization of new ion-imprinted polymer for separation and preconcentration of uranyl (UO2(2+)) ions.

UO(2)(2+) ion-imprinted polymer materials used for solid-phase extraction were prepared by copolymerization of a ternary complex of uranyl ions with styrene and divinyl benzene in the presence of 2,2'-azobisisobutyronitrile. The imprinted particles were leached by HCl 6M. Various parameters in polymerization steps such as DVB/STY ratio, time of polymerization and temperature of polymerization were varied to achieve the most efficient uranyl-imprinted polymer. X-ray diffraction (XRD), infra-red spectroscopy (IR), thermo gravimetric analysis (TGA), UV-vis and nitrogen sorption were used to characterize the polymer particles. The XRD results showed that uranyl ions were completely removed from the polymer after leaching process. IR Analysis indicated that the N,N'-ethylenebis(pyridoxylideneiminato) remained intact in the polymer even after leaching. Some parameters such as pH, weight of the polymer, elution time, eluent volume and aqueous phase volume which affects the efficiency of the polymer were studied.

Synthesis of nano-pore samarium (III)-imprinted polymer for preconcentrative separation of samarium ions from other lanthanide ions via solid phase extraction.

A batch process was developed to separate samarium ions from some lanthanide ions by a novel solid phase which was prepared via the ion-imprinting technique. The samarium (III) ion-imprinted polymer (IIP) particles were synthesized by preparing the ternary complex of samarium ions with 5,7-dichloroquinoline-8-ol (DCQ) and 4-vinylpyridine (VP). Then, thermally copolymerization with styrene (functional monomer, STY) and divinylbenzene (cross-linking monomer, DVB) followed in the presence of 2-methoxy ethanol (porogen) and 2,2'-azobisisobutyronitrile (initiator, AIBN). The imprinted ion was removed by stirring the above particles with 50% (v/v) HCl to obtain the leached IIP particles. Moreover, control polymer (CP) particles were similarly prepared without the samarium ions. The unleached and leached IIP particles were characterized by X-ray diffraction (XRD), infra-red spectroscopy (IR), thermo gravimetric analysis (TGA) and scanning electron microscopy (SEM). Finally, preconcentration and selectivity studies for samarium and the other lanthanide ions were carried out. The preconcentration of the samarium (III) traces was studied during rebinding with the leached IIP particles as a function of pH, the weight of the polymer material, the preconcentration and the elution times, the eluent volume and the aqueous phase volume. These studies indicated that the samarium (III) amount as low as 1 microg, present in 200 mL, could be preconcentrated into 25 mL of 1.0 M HCl.

Novel method for the fast determination of ultra trace amount of nortriptyline in its pharmaceutical formulations by fast fourier transform continuous cyclic voltammetric technique at Au microelectrode in flowing solutions.

In this work a novel method for the determination of nortriptyline in flow-injection systems has been developed. The proposed method was used for the fast determination of nortriptyline in its pharmaceutical formulations. The developed technique is very simple, precise, accurate, time saving, and economical, compared to all of the previously reported methods. The effects of various parameters on the sensitivity of the method were investigated. The best performance obtained at pH value of 2, scan rate value of 30 V/s, accumulation potential of 400 mV, and accumulation time of 0.5 s. The proposed method has some advantages over other reported methods such as, no need for the removal of oxygen from the test solution, a subnanomolar detection limit, and finally the method is sufficiently fast for the determination of any such compound, in a wide variety of chromatographic methods. The potential waveform, consisting of the potential steps for cleaning, accumulation and potential ramp of analyte, was continuously applied on an Au disk microelectrode (12.5 microm in radius). The detection limit of the method was 2.0 x 10(-11) M. The relative standard deviation of the method at 1.2 x 10(-8) M was 2.1% for eight runs.

Sub-second adsorptive fast Fourier transform coulometric technique as a novel method for the determination of nanomolar concentrations of sodium valproate in its pharmaceutical preparation in flowing solution systems.

In this work, a novel electrochemical technique has been developed for determination of nanomolar concentration of sodium valproate in flow-injection systems. The detection was done by adsorptive fast Fourier transform coulometric (AFFTC), in which the potential waveform consists of potential steps for cleaning, accumulation, and a potential ramp that was continuously applied on an Au disk microelectrode. Moreover, a special computer program is introduced based on numerical method, for calculation of the analyte signal (which is the partial and total charge exchanges at the electrode surface) and noise reduction. The optimum parameters were: pH value of 2.0, scan rate value of 40 Vs(-1), accumulation potential of 200 mV and accumulation time of 0.3 s. Detection limit of the method for sodium valproate was 9.0x10(-9) M. The relative standard deviation of the method at 1.3x10(-7) M was 2.0% for 10 runs.