Radiolabeling and biological evaluation of losartan as a possible cardiac imaging agent

A procedure was developed for preparing high radiochemical purity ^99m Tc-Losartan in a yield of about 90%. The optimal reaction conditions are as follows: 100 μg of Losartan, 50 μg of SnCl₂·2H₂O, 150 μL of phosphate buffer (pH 7), room temperature (25 ± 1°C), reaction time 5 min. Under these conditions, the radiochemical yield up of ^99m Tc-Losartan reaches 98%. The radiochemical yield and purity of the labeled product were determined by electrophoresis and paper chromatography. Biodistribution studies were carried out in normal Albino Swiss mice at different time intervals after administration of ^99m Tc-Losartan. The labeled compound cleared from the systematic circulation within 3 h after administration, and the majority of organs showed significant decrease in the uptake of ^99m Tc-Losartan. The heart uptake of ^99m Tc-Losartan was sufficiently high for using this agent as myocardial imaging agent.     

Radioiodination of pindolol as a β-adrenergic receptor using different oxidizing agents

A simple, fast, and efficient method was developed for preparing radioiodinated ¹²⁵I-pindolol (¹²⁵IPIN) using different oxidizing agents. ¹²⁵I-PIN was prepared by the reaction between Na¹²⁵I and pindolol using iodogen, Chloramine-T, N-bromosuccinamide, or H₂O₂ as an oxidizing agent at pH 7. The reaction proceeds well within 30 min at room temperature (20–25°C). The radiochemical yield was determined by TLC using chloroform-acetic acid-water (15: 4: 1) as developing solvent and by HPLC using reversed-phase RP18 column and acetonitrile-0.1 M ammonium bicarbonate (pH 7.5) (1: 1) as the mobile phase at a flow rate of 1 mL min^?1. The radiochemical yield with the above oxidants was found to be 85, 93, 96.5, and 97.5%, respectively, with the radiochemical purity of ¹²⁵I-PIN over 99.9%.     

Electrophilic iododestannylation of <Emphasis Type="Italic">N</Emphasis>-(4-(2-azanorborn-2-yl)butyl)-4-trimethylstannylbenzamide as a route to a novel radioiodinated compound for malignant melanoma

N-(4-(2-Azanorborn-2-yl)butyl)-4-[¹²⁵I]iodobenzamide was prepared by the reaction of its trimethylstannyl precursor with Na¹²⁵I in the presence of various oxidizing agents such as lactoperoxidase, Chloramine T, and Iodogen. The effect of reaction parameters such as temperature, reaction time, oxidizing agent concentration, pH, and substrate concentration was examined. The stability of the labeled product was evaluated. Chromatographic analysis of the reaction mixture by TLC using ethanol: ethyl acetate (1: 1) and by HPLC using methanol: water (55: 45) as eluent showed that the optimum radiochemical yield of the final product is 94% and the radiochemical purity is 99%. Also HPLC chromatographic analysis showed that the content of undesired by-products, especially of chlorinated products, in case of Chloramine T was higher than that in case of other oxidizing agents. With the lactoperoxidase method, the amount of undesired by-products was minimal and, therefore, the radiochemical purity was high.     

Preparation, quality control, and biodistribution of 99mTc-rufloxacin complex as a model for detecting sites of infection

With the aim of the development of a new radiopharmaceutical for infection imaging, able to differentiate between septic and aseptic inflammations, ^99m Tc-rufloxacin was obtained. Its radiochemical yield reaches 93.4 ± 3% under optimum conditions (addition of ^99m TcO₄ — to a solution containing 50 mg of rufloxacin and 50 μg of SnCl₂·2H₂O at pH 6). ^99m Tc-rufloxacin biodistribution studies in Albino mice bearing septic and aseptic inflammation models showed that ^99m Tc-rufloxacin is able to differentiate between septic and aseptic inflammations.     

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.     

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.     

Modification of Automatic Synthesis of [<Superscript>18</Superscript>F]Fluoromisonidazole on a GE TracerLAB Fx F-N Synthesis Module

A procedure for preparing 1-(2-hydroxy-3-[¹⁸F]fluoropropyl)-2-nitroimidazole ([¹⁸F]fluoromisonidazole, [¹⁸F]FMISO) on a commercially available GE TracerLAB Fx F-N synthesis module was developed. The product obtained meets all the requirements of the European Pharmacopoeia (8th ed.) for clinical use. Its decay-corrected radiochemical yield is 59 ± 4% (n = 5).     

Comparative Biological Evaluation of <Superscript>99<Emphasis Type="Italic">m</Emphasis></Superscript>Tc-Timonacic Acid Prepared Using Different Reducing Agents as a Complex for Hepatobiliary Imaging

Timonacic acid (TCA) was labeled with ^99mTc in the presence of three different reducing agents: NaBH₄, Na₂S₂O₄, and SnCl₂·2H₂O. The optimum conditions were as follows: with Na₂S₂O₄, pH 8, 7 mg of Na₂S₂O₄, room temperature, 2 mg of TCA, 30 min (radiochemical yield 98 ± 0.3%, complex was stable for 24 h); with NaBH₄, pH 8, 10 mg of NaBH₄, room temperature, 2 mg of TCA, 30 min (radiochemical yield 95 ± 0.3%, complex was stable for 6 h). The biodistribution of the complex in mice was studied. The liver uptake depends on the reducing agent used, reaching in 30 min 33.5 ± 0.3, 18.4 ± 0.18, and 22.3 ± 0.3% ID/g for the complexes prepared using Na₂S₂O₄, NaBH₄, and SnCl₂·2H₂O, respectively.     

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.     

99m Tc-sulfadimidine as a potential radioligand for differentiation between septic and aseptic inflammations

Sulfadimidine, a bacteriostatic drug blocking folic acid synthesis, was labeled with ^99m Tc producing a yield of about 90%. The optimum conditions required to obtain 90% yield of the ^99m Tc complex were as follows: 500 μg of sulfadimidine, 100 μg of SnCl₂·2H₂O, 5 min, room temperature (25 ± 1°C), pH 4 (0.5 M citrate buffer). The radiochemical purity of the labeled compound was determined using paper and thin-layer chromatography. Biodistribution study in normal mice showed high uptake of the ^99m Tc complex in stomach and intestine. The ratio of the uptake of the ^99m Tc complex in muscles infected with E. coli to that in normal mice was about 2, 1.5 and 1.4 at 15, 90, and 180 min post injection, respectively, whereas for the muscles inflamed with heat-killed E. coli or sterile turpentine oil the difference from the normal muscles was insignificant.     

Radiodiagnosis of peptic ulcer with technetium-99m-pantoprazole

Pantoprazole, antiulcer drug, was labeled with ^99m Tc to obtain an agent for ulcer imaging. The radiochemical yield of ^99m Tc-Pantoprazole reaches approximately 96.5%. The optimum conditions are as follows: pH 10, 75 μg of tin chloride, 30 min, and 2 mg of the substrate. ^99m Tc-Pantoprazole was stable for 3 h. Intravenous biodistribution studies of ^99m Tc-Pantoprazole revealed high concentration in the stomach ulcer, reaching about 27.2% of the total injected dose at 30 min post injection. This concentration of ^99m Tc-Pantoprazole in stomach ulcer makes this agent promising for stomach ulcer imaging.     

Radiochemical and biological characterization of 99m Tc-piracetam for brain imaging

Experiments on piracetam labeling with ^99m Tc were performed. The radiochemical yield of 97% was obtained under the optimum conditions: pH 6, SnCl₂·2H₂O as reducing agent, room temperature, 30 min. In vivo biodistribution studies showed that the initial brain uptake correlated fairly well with the brain binding affinity of the compound. The brain uptake of ^99m Tc-piracetam was as high as 6, 12.3, 5.3, and 3.3% per gram tissue at 5, 30, 60, and 120 min post injection, respectively. ^99m Tc-piracetam shows promise in radioreceptor assays of neuroleptic drug levels and, in the labeled form, for brain imaging.     

Synthesis of 99m Tc-L-carnitine as a model for tumor imaging

An L-carnitine derivative labeled with ^99m Tc was prepared. It is effective in tumor imaging. The labeling was done using SnCl₂ as a reducing agent. The optimum conditions required to label 25 ??g of L-carnitine were as follows: 100 ??g of SnCl₂, 30 min reaction time, room temperature, pH 7 (0.5 M phosphate buffer). The radiochemical purity of the labeled compound was determined by paper chromatography. The yield was about 93%. About 2.5 × 10⁶ Ehrlich ascites carcinoma (EAC) cells were injected intraperitoneally to produce ascites and intramuscularly in the right thigh to produce solid tumor in female mice. Biodistribution studies were carried out by injecting a solution of ^99m Tc-L-carnitine into normal and tumor-bearing mice. The uptake in ascites and in solid tumor was over 5% of the injected dose per gram tissue at 4 h post injection. These data revealed localization of the tracer in the tumor tissues with high percentage sufficient to use ^99m Tc-L-carnitine as a promising tool for diagnosis of tumor.     

Synthesis of 2-[18F]Fluoro-L-tyrosine and comparative study of its uptake by rat glioma 35 tumor and by induced inflammation focus in experimental animals

2-[¹⁸F]Fluoro-L-tyrosine (2-[¹⁸F]FTYR), a labeled fluorinated analog of tyrosine, was prepared using chiral phase-transfer catalysis. The radiochemical yield of 2-[¹⁸F]FTYR corrected for radioactive decay was 25±6% (n = 15) at a synthesis time of 110–120 min, including semipreparative HPLC purification. The radiochemical and chemical purity of the product exceeded 99%, and the enantiomeric purity was 98.2±0.7% (n = 15). The uptake of 2-[¹⁸F]FTYR by tumors and abscesses in laboratory animals was studied. The ratios of radioactivity uptake by tumor or imflamed tissue to that of an intact muscle tissue were calculated. Within the time of experiment, the tumor/muscle ratio exceeds the abscess/muscle ratio. The results obtained allow 2-[¹⁸F]FTYR to be considered as potentially useful radiotracer for differential diagnostics of tumors and inflammations by PET.     

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.     

Synthesis and spectral properties of colloidal Nd doped NaYF4 nanocrystals

Transparent, chloroform dispersed α-NaYF₄ nanocrystals doped with neodymium ions were synthesized and characterized. XRD and TEM measurement confirmed cubic structure of α-NaYF₄ of the nanoparticles (NPs). The absorption and emission spectra as well as ⁴F_3/2 level fluorescence decay curves were measured in order to estimate the influence of Nd³⁺ concentration in the matrix on the optical properties of the NPs. With the increase of Nd³⁺ doping level, the Judd-Ofelt Ω₄ parameter as well as the spectroscopic Nd³⁺ parameter X_Nd = Ω₄/Ω₆ was growing. In the same time the Ω₂ and Ω₆ were decreasing. Theoretical luminescence lifetimes of the ⁴F_3/2 level equal to ∼300 μs were also calculated and compared with the experimental values to quantify the concentration quenching. Based on this comparison, quantum efficiency was found to vary systematically between ∼100% and 4% for Nd³⁺ content increasing from 2 up to 25%.     

Effect of substrate temperature and amount of strengthening phase on density and mechanical properties of thick Ni-ZrO2 condensates

Dispersion-strengthened Ni-ZrO₂ condensates 1–2 mm thick were produced by separate electron beam evaporations of nickel and the strengthening addition of ZrO₂ from self-contained sources in a vacuum of 1 × 10^-4 - 5 × 10^-5 Torr. Deposition of the vapor mixture was performed at substrate temperatures of 650, 850 and 1100 °C; this allowed us to vary the size of the ZrO₂ particles between 120 and 1300 Å. The content of the second phase varied between 0 and 6 vol.%. The density of the two-phase condensates was determined as a function of substrate temperature and the amount of the second phase. The short-time tensile properties of the condensates were studied at test temperatures of 20, 700 and 1000 °C. The dependences of the density and mechanical properties of the condensates on substrate temperature and the amount and size of the second phase particles were established. The yield strengths of two-phase condensed materials are discussed on the basis of Orowan's dislocation model as modified by Ashby. It is shown that the 0.2% offset yield strength of two-phase Ni-ZrO₂ condensates at 20 °C can be expressed by the relation σ_0.2 = σ_{OR + 1.35 × 10³}f, where σ_OR = 2τ, τ is the yield strength according to Orowan and f is the volumetric fraction of ZrO₂.     

Novel Tm-doped fluorotellurite glasses with enhanced quantum efficiency

In this paper, new highly Tm³⁺-doped tellurite glasses with host composition 75TeO₂-xZnF₂-yGeO₂-12PbO-3Nb₂O₅ [x(5-15), y(0-5) mol%] are presented and compared to the Tm-doped tellurite glasses based on the traditional host composition: 75TeO₂-20ZnO-5Na₂O mol%. Enhanced quantum efficiency from ³F₄ level was observed for the proposed glasses and thermal stability and viscosity values make them suitable for optical fiber drawing. Besides the host composition, substantial influence of Tm³⁺ concentration on luminescence and lifetime of excited ³F₄ and ³H₄ states were discussed.     

Radiosynthesis of 99m Tc-labeled novobiocin dithiocarbamate complex as a potential Staphylococcus aureus infection radiotracer

The ^99m Tc complex with dithiocarbamate derivative of novobiocin, ^99m Tc(CO)₃-NBND, was prepared using the [^99m Tc(CO)₃(H₂O)₃]⁺ precursor. The complex was examined to evaluate its radiochemical permanence in saline and serum, in vitro bacterial uptake, and biodistribution in male Wistar rats (MWR). The ^99m Tc(CO)₃-NBND complex showed more than 90% radiochemical stability in saline for up to 4 h. The complex gave maximum stability of 99.10 ± 0.24% in saline after 30 min of reconstitution. In serum, 12.40% side products are accumulated within 16 h. The ^99m Tc(CO)₃-NBND complex showed 76.80 ± 0.90% in vitro binding with Staphylococcus aureus (S. aureus). In infected MWR muscles, ^99m Tc(CO)₃-NBND uptake was approximately 6 times higher than in inflamed and normal muscles. High stability of ^99m Tc(CO)₃-NBND in saline and serum, in vitro binding with live S. aureus, and specific higher uptake in the infected (live S. aureus) muscles make it a potential infection radiotracer.     

Preparation of Fentanyl Labeled with Carbon-14

A convenient synthetic pathway for ¹⁴C labeling of fentanyl [N-(1-phenethyl-4-piperidinyl)- propionanilide], a widely used narcotic analgesic agent, with good radiochemical yield was developed.