Advanced prospects for the preparation of zirconium [<Superscript>99</Superscript>Mo]molybdate(VI) gel from diluted reactants and <Superscript>99<Emphasis Type="Italic">m</Emphasis> </Superscript>Tc elution performance

Zirconium [⁹⁹Mo]molybdate(VI) gel (ZrMo) was prepared from dilute mixed solutions of zirconium oxychloride and [⁹⁹Mo]molybdate at pH 4.7. Paramolybdate(VI) anions were attracted to the positively charged surface of zirconia(IV) particulates (PZC at pH 7.2). The postulated reaction mechanism and gel formula were verified by radiometric analysis, X-ray diffraction, scanning electron microscopy, TGA, DTA, IR spectroscopy, and X-ray fluorescence analysis. ^99mTc elution from ZrMo dried at 50 and 200°C was investigated. Reproducibly high ^99mTc elution yield with high levels of radionuclidic, radiochemical, and chemical purity was achieved from the gel dried at 50°C. Correlation between structural properties of ZrMo and ^99mTc elution performance was discussed.     

Synthesis and Stability of New Nitrophenol Complexes of <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc as Possible Hypoxia Imaging Radiopharmaceuticals

Seven new nitrophenol derivatives were synthesized; their ^99mTc complexes (N₂OS chelates), which are possible hypoxia tumor imaging agents, were prepared by the reaction with [^99mTc]NaTcO₄ in the presence of SnCl₂ at pH 10. The in vitro biostabilty of the complexes was evaluated. The purity and stability (in human and rat serum) of the complexes were evaluated by chromatographic methods (TLC, HPLC). The most stable (for more than 6 h) is the complex of ^99mTc with 3-[3′-N-(2″-hydroxy-5″-nitrobenzylamino)-2′-hydroxypropyl]-1-methylthiourea.     

Preparation and biological evaluation of <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc-timonacic acid as a new complex for hepatobiliary imaging

Timonacic acid (TCA) was successfully labeled with ^99m Tc. The influence exerted on the reaction by the substrate and reducing agent concentrations, pH of the reaction mixture, and reaction time was examined, and in vitro stability of ^99m Tc-TCA was evaluated. The maximum labeling yield was 98.5 ± 0.6%. The complex was stable throughout the working period (6 h). A study of in-vivo biodistribution in mice showed that the maximum uptake of ^99m Tc-TCA in the liver was 22.3 ± 0.3% of the injected activity per gram of the tissue or organ (% ID/g) at 30 min post injection. The clearance from the mice appeared to proceed via the circulation mainly through the kidneys and urine (approximately 56% of the injected dose at 1 h after injection). The liver uptake of ^99m Tc-TCA is higher than that of ^99m Tc-UDCA (ursodeoxycholic acid); therefore, ^99m Tc-TCA shows more promise for liver SPECT.     

Formulation and Biodistribution of <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc-Dacarbazine,a Radioligand for Neoplasm Imaging

A method for preparing ^99mTc-Dacarbazine, a potential cancer diagnostic agent, was developed. The method is based on direct labeling of Dacarbazine with ^99mTc in the presence of stannous chloride as reducing agent. The reaction conditions were optimized to obtain the radiochemical yield of ^99mTc-Dacarbazine higher than 90%. The biodistribution of ^99mTc-Dacarbazine in normal and tumor-bearing Albino Swiss mice was studied. ^99mTc-Dacarbazine has a high tumor affinity and shows promise for cancer imaging. Quantitative relationship between the optimized structures and computed molecular properties related to Dacarbazine binding sites was analyzed using molecular modeling.     

Preclinical evaluation of <Superscript>99<Emphasis Type="Italic">m</Emphasis> </Superscript>Tc-histidine as a possible tumor imaging agent

Radiolabeling of histidine (Hist), an essential amino acid, with ^99mTc was performed. The radiochemical yield higher than 95% was achieved with stannous chloride as a reducing agent. Factors affecting the radiochemical yield (histidine amount, stannous chloride amount, reaction time, pH of the reaction mixture) were studied in detail, and the reaction conditions were optimized. In vitro stability of the radiolabeled complex was checked, and it was found to be stable for up to 6 h. ^99mTc-Hist was injected intravenously into normal and tumor-bearing mice. Biodistribution studies revealed that the ^99mTc-Hist uptake in tumor sites was 10 and 16% ID/g in ascites and 7 and 9.2% ID/g in thigh solid tumor at 60 and 120 min post injection, respectively. The amount of ^99mTc-Hist in ascites and solid tumor increased with time and then decreased slowly. Thus, ^99mTc-Hist can be used as a potential agent for imaging tumor sites.     

Optimized chromatographic separation and biological evaluation of <Superscript>99<Emphasis Type="Italic">m</Emphasis> </Superscript>Tc-clarithromycin for infective inflammation diagnosis

Clarithromycin antibiotic was labeled with technetium-99m by adding ^99mTc to clarithromycin in the presence of SnCl₂·2H₂O. The radiochemical yield of ^99mTc-clarithromycin was determined by chromatographic methods. Gel chromatographic method was investigated for separation of the reaction mixture using different eluents including NaCl and phosphate, citrate, and carbonate buffer solutions. Also, free ^99mTcO₄^- and ^99mTc-clarithromycin were efficiently separated by reversed-phase HPLC on RP18 column. The maximum radiochemical yield reached 98 ± 0.2%. ^99mTc-clarithromycin is stable for 6 h. Biological distribution of ^99mTc-clarithromycin was studied for mice with the infection in the left thigh induced using Staphylococcus aureus. The target-to-nontarget (T/NT) ratio for ^99mTc-clarithromycin was found to be 7.33 ± 0.13 at 2 h after intravenous injection, with the subsequent gradual decline. This value is higher than that of commercially available ^99mTc-ciprofloxacin. The abscess to normal muscle ratio shows that ^99mTc-clarithromycin can be successfully used for infection imaging, allowing differentiation between bacterial infection and sterile inflammation.     

Influence of Sn<Superscript>2+</Superscript> concentration on complexation of <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc with potassium sodium hydroxyethylidenediphosphonate

Kinetics of formation of a ^99m Tc complex with potassium sodium hydroxyethylidenediphosphonate (KNaHEDP) was studied. Since the Tc reduction competes with the Tc reoxidation at low Sn²⁺/Sn⁴⁺ concentration ratio, the reaction accelerates with increasing Sn²⁺ concentration from 1 to 10 μg ml^?1. At higher Sn²⁺ concentrations, Sn²⁺ ions have no effect on the complexation rate, since the concentration of reduced technetium becomes optimal for effective formation of the technetium complex with the ligand. More than 95% of ^99m Tc is bound into the complex at the Sn²⁺ concentration higher than 20 μg ml^?1. A high degree of Tc complexation is observed immediately after mixing the reactants and is maintained for 24 h. The rate and degree of ^99m Tc complexation with KNaHEDP are independent of the ligand concentration in the reaction mixture, varied from 5 to 10 mg ml^?1. At higher ligand concentration (25 mg ml^?1), the rate of formation of the ^99m Tc-KNaHEDP complex does not change, but its stability decreases.     

Radiodiagnosis of peptic ulcer with technetium-99<Emphasis Type="Italic">m</Emphasis>-labeled esomeprazole

Esomeprazole was labeled with ^99m Tc in high (up to ~98.0%) radiochemical yield. The optimum conditions are as follows: pH 8, 50 μg of SnCl₂·2H₂O, 30 min, and 2 mg of the substrate. The complex is stable for 8 h. The reaction mixture was separated by gel chromatography using such eluents as NaCl solution and, phosphate, citrate, and carbonate buffer solutions. Free ^99m TcO ₄ ^– and the complex were also efficiently separated by reversed-phase HPLC, paper chromatography, and electrophoreses. Intravenous biodistribution studies of ^99m Tc-esomeprazole complex showed high uptake in the stomach ulcer, reaching about 30.5% ID/g at 1 h post injection. Such a high ^99m Tc-esomeprazole uptake makes this agent promising for stomach ulcer imaging.     

Synthesis of <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc-Radiolabeled Uridine as a Potential Tumor Imaging Agent

Uridine, a pyrimidine nucleoside essential for the synthesis of RNA and biomembranes, was radiolabeled with ^99mTc to obtain a potential tumor imaging agent. The maximal radiochemical yield of about 96.5%, as determined by paper chromatography and instant thin-layer chromatography, was reached under the following optimum conditions: 1 mg of uridine, 20 μg of SnCl₂·2H₂O as reducing agent, 20 mg of mannitol as a stabilizer, and pH 8. ^99mTc-uridine is stable in vitro at room temperature for up to 6 h post labeling. The biodistrbution study in tumor-bearing mice shows high target-to-nontarget ratio. These results match with the high docking score of the complex on uridine phosphorylase enzyme. ^99mTc-uridine shows promise as a tumor imaging agent.     

<Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc-Oxiracetam as a Potential Agent for Diagnostic Imaging of Brain: Labeling,Characterization, and Biological Evaluation

Oxiracetam was labeled with ^99mTc using sodium dithionite (Na₂S₂O₄) as a reducing agent. The influence exerted on the labeling yield by the amounts of the reducing agent and substrate, pH, temperature, and reaction time was studied to optimize the labeling process. Biodistribution studies show that the ^99mTcoxiracetam complex is suitable as a highly selective tracer for brain imaging.     

Design,synthesis, <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc labeling,and biological evaluation of a novel pyrrolizine derivative as potential anti-inflammatory agent

The design and synthesis of ethyl 4-(6-amino-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamido)-benzoate (KH16) were discussed, and its structure was determined. The anti-inflammatory activity of a new compound was evaluated using in vitro cyclooxygenase (COX) inhibitory assay. KH16 exhibits higher selectivity to COX-2 than to COX-1 with the selectivity index of 3.46. KH16 was labeled with ^99mTc with the maximum radiochemical yield of ^99mTc-KH16 of 90.5 ± 1.5%. Biodistribution of ^99mTc-KH16 in normal, infected, and inflamed mice was studied. The uptake in inflamed muscle was higher than that in normal muscle throughout the examined time interval. This work is a step ahead in the direction of using pyrrolizine derivatives for site-specific delivery to the inflamed tissue.     

Interaction of neptunium and technetium with UO<Subscript>2+<Emphasis Type="Italic">x</Emphasis></Subscript>

Interaction of uranium dioxide with highly mobile radionuclides ²³⁷Np and ⁹⁹Tc was studied under oxidative conditions. Sorption of these radionuclides at different pH was measured, and the mechanism of redox reaction occurring in the course of their sorption were determined. In alkaline solution, Np(V) is reduced on the UO_2+x surface and is sorbed in the form of tetravalent species. In neutral solutions, Np is sorbed in the form of Np(V). This is due to the fact that the stoichiometry of the UO_2+x surface corresponds to U₄O₉. In acid solution, U(VI) is leached to form surface UO₂. Although the free surface area of a UO_2+x sample is low, the Np distribution coefficients K _d at pH > 6 are relatively high: log K _d > 2. Unlike Np, Tc(VII) is not reduced on the UO_2+x surface. However, the sorption capacity of uranium dioxide for Tc(IV) is high.     

Radiochemical and biological characterization of <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc-oxiracetam as a model for brain imaging

^99mTc-oxiracetam was prepared. It can be used as a radiotracer for brain imaging. Under the optimum conditions (0.5 mg of oxiracetam, 50 μg of SnCl₂·2H₂O, pH 7, room temperature, 30 min), the radio-chemical yield determined by chromatographic methods reached 96%. Biodistribution studies with mice showed that the brain uptake of the complex was 5.1% injected dose per gram (% ID/g) at 5 min post injection. In this parameter, the complex surpasses the commercially available ^99mTc-ECD (4.7% ID/g) and ^99mTc-HMPAO (2.25% ID/g).     

Radiolabeling,quality control,and biodistribution of <Superscript>99m</Superscript>Tc-sulfadiazine as an infection imaging agent

Abstract—Sulfadiazine (antibiotic used for treating bacterial infections) was labeled with ^99mTc with the aim of the development of a new radiopharmaceutical for infection imaging. The influence of the reaction parameters such as the substrate and SnCl₂·2H₂O concentrations, pH of the reaction mixture, and reaction time on the labeling yield was examined, and the labeling conditions were optimized. The maximum radiochemical yield of ^99mTc-sulfadiazine (94.7%) was obtained by using 50 µg of SnCl₂·2H₂O and 1 mg of sulfadiazine at pH 5. The radiochemical purity of the labeled compound was evaluated by ITLC and HPLC. The biological distribution of ^99mTc-sulfadiazine in mice with experimentally induced Staphylococcus aureus infection in the right thigh was studied, and the bacterial infected thigh/normal thigh (target-to-nontarget, T/NT) ratio was evaluated. The T/NT ratio for ^99mTc-sulfadiazine was found to be 3.6, which is comparable to the commercially available ^99mTc-ciprofloxacin (3.8), indicating that ^99mTc-sulfadiazine can be used for infection imaging.     

Preparation and properties of Pr<Superscript>3+</Superscript>/Ce<Superscript>3+</Superscript>:YAG phosphors using triethanolamine as dispersant and pH regulator

Pr³⁺/Ce³⁺:YAG precursors were co-precipitated using triethanolamine as dispersant and pH regulator. The different dosages of triethanolamine (D) vs. the properties of Pr³⁺/Ce³⁺:YAG phosphors were discussed. When D = 0.5 vol%, the pH of titration process was controlled in the range of ～7.94–8.16 to guarantee the uniform distribution of Al, Y, Ce and Pr in the precursors. The relatively higher pH could decrease the loss of Ce and Pr in the precursors and increase the particle size of the obtained powders, which was beneficial to the enhancement of luminescent intensity. Therefore, the precursors directly converted to pure-phase YAG at 900°C, and the phosphors calcined at 1000°C showed the best dispersity due to the dispersion effect of triethanolamine and the most excellent luminescent property. When D ≥ 2 vol%, although pure-phase YAG was detected, the emission intensity of the phosphors decreased due to the decrease of dispersity and purity. Moreover, the co-doped Pr³⁺ enhanced the red emission of Pr³⁺/Ce³⁺:YAG phosphors.     

Labeling and biological evaluation of <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc-tricarbonyl-chenodiol for hepatobiliary imaging

^99m Tc-tricarbonyl-labeled chenodiol (chenodeoxycholic acid, CDCA) intended for hepatobiliary imaging was prepared by 30-min heating at 100°C with a radiochemical yield of >98%. The radiolabeling yield and stability of the complex were evaluated using different chromatographic techniques. Biodistribution studies in Albino Swiss mice at different time intervals after administration of the complexes showed that the maximum uptake of the complexes in the liver was 35.5 ± 0.25% ID/g at 30 min post injection. ^99m Tc-tricarbonyl- CDCA shows promise for hepatobiliary imaging.     

Asymmetric synthesis of 6-<Superscript>18</Superscript>F-<Emphasis Type="Italic">L</Emphasis>-FDOPA using chiral Nickel(II) complexes

A new procedure was suggested for asymmetric synthesis of of 6-[¹⁸F]fluoro-3,4-L-dihydroxyphenylalanine (6-¹⁸F-L-FDOPA), an important radiotracer for studies of the dopaminergic system by positron emission tomography (PET). The key step of the synthesis is stochiometric asymmetric alkylation of chiral Ni(II) complexes using 3,4-methylenedioxy-6-[¹⁸F]fluorobenzyl bromide as alkylating agent. A series of Ni(II) complexes containing various substituents in the benzyl group were tested. The highest enantiomeric purity of 6-¹⁸F-L-FDOPA was attained with the complex derived from (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide, Ni-DCBPB-Gly, under mild alkylation conditions (CH₂Cl₂, 40°C, potassium tert-butylate as base). Such conditions are favorable from the viewpoint of synthesis automation. The radiochemical yield of 6-¹⁸F-L-FDOPA corrected for the radioactive decay was 10–15% at a synthesis time of 120 min, including purification by semipreparative HPLC. The radiochemical and chemical purity of the product exceeded 99%, and the enantiomeric purity was as high as 95%, meeting the requirements for using 6-¹⁸F-L-FDOPA in PET practice.     

Cu<Superscript>2+</Superscript> and Al<Superscript>3+</Superscript> co-substituted cobalt ferrite: structural analysis,morphology and magnetic properties

Cu–Al substituted Co ferrite nanopowders, Co_1?x Cu _x Fe_2?x Al _x O₄ (0.0 ≤ x ≤ 0.8) were synthesized by the co-precipitation method. The effect of Cu–Al substitution on the structural and magnetic properties have been investigated. X-ray diffraction (XRD) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM) and vibrating sample magnetometer (VSM) are used for studying the effect of variation in the Cu–Al substitution and its impact on particle size, magnetic properties such as M _s and H _c . Cu–Al substitution occurs and produce a secondary phase, α-Fe ₂ O ₃. The crystallite size of the powder calcined at 800 ^°C was in the range of 19–26 nm. The lattice parameter decreases with increasing Cu–Al content. The nanostructural features were examined by FESEM images. Infrared absorption (IR) spectra shows two vibrational bands; at around 600 (v ₁) and 400 cm ^?1 (v ₂). They are attributed to the tetrahedral and octahedral group complexes of the spinel lattice, respectively. It was found that the physical and magnetic properties have changed with Cu–Al contents. The saturation magnetization decreases with the increase in Cu–Al substitution. The reduction of coercive force, saturation magnetization and magnetic moments are may be due to dilution of the magnetic interaction.     

Influence of isovalent and heterovalent substitution for Bi<Superscript>3+</Superscript> and Fe<Superscript>3+</Superscript> on the properties of Bi<Subscript>2</Subscript>Fe<Subscript>4</Subscript>O<Subscript>9</Subscript>-based solid solutions

Bi_2–хLa_хFe₄O₉ and Bi₂Fe_4–2xTi_xCo_xO₉ ferrites have been prepared by solid-state reactions at a temperature of 1073 K. X-ray diffraction data indicate that, in the Bi_2–хLa_хFe₄O₉ system, the limiting degree of La³⁺ substitution for Bi³⁺ ions in Bi₂Fe₄O₉ does not exceed 0.05 and that the limiting degree of substitution in the Bi₂Fe_4–2xTi_xCo_xO₉ system lies in the range 0.05 < x < 0.1. The specific magnetization and specific magnetic susceptibility of the samples have been measured at temperatures from 5 to 300 K in a magnetic field of 0.86 T. The field dependences of magnetization obtained for the Bi_2–хLa_хFe₄O₉ and Bi₂Fe_4–2xTi_xCo_xO₉ ferrites at temperatures of 300 and 5 K demonstrate that partial isovalent substitution of La³⁺ for Bi³⁺ ions in Bi₂Fe₄O₉ and heterovalent substitution of Ti⁴⁺ and Co²⁺ ions for two Fe³⁺ ions leads to partial breakdown of the antiferromagnetic state and nucleation of a ferromagnetic state.     

Hybrid <Superscript>99m</Superscript>Tc-magnetite tracer for dual modality sentinel lymph node mapping

Accuracy of sentinel lymph node identification using radioactive tracers in non-superficial cancers can be limited by radiation shine through and low spatial resolution of detection systems such as intraoperative gamma probes. By utilising a dual radioactive/magnetic tracer, sensitive lymphoscintigraphy can be paired with high spatial resolution intraoperative magnetometer probes to improve the accuracy of sentinel node detection in cancers with complex multidirectional lymphatic drainage. Dextran-coated magnetite nanoparticles (33?nm mean hydrodynamic diameter) were labelled with ^99mTc and applied as a lymphotropic tracer in small and large animal models. The dual tracer could be radiolabelled with 98?±?2% efficiency after 10?min of incubation at room temperature. Biodistribution studies of the tracer were conducted in normal rats (subdermal and intravenous tail delivery, n?=?3) and swine (subdermal hind limb delivery, n?=?5). In rats the dual tracer migrated through four tiers of lymph node, 20?min after subdermal injection. Results from intravenous biodistribution test for radiocolloids demonstrated no aggregation in vivo, however indicated the presence of some lower-molecular weight radioactive impurities (^99mTc-dextran). In swine, the dual tracer could be effectively used to map lymphatic drainage from hind hoof to popliteal and inguinal basins using intraoperative gamma and magnetometer probes. Of the eight primary nodes excised, eight were positively identified by gamma probe and seven by magnetometer probe. The high-purity dual tracer shows early promise for sentinel node identification in complex lymphatic environments by combining sensitive preoperative lymphoscintigraphy with a high-resolution intraoperative magnetometer probe.

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