Synthesis of 99m Tc-erythromycin complex as a model for infection sites imaging

Labeling of erythromycin with ^99m Tc using SnCl₂·2H₂O as a reducing agent was investigated. Dependence of the yield of ^99m Tc-erythromycin complex on the concentrations of erythromycin and reducing agent, on pH, and on the reaction time was studied. 97% labeling yield of ^99m Tc-erythromycin complex was achieved by performing the reaction with 1.5 mg of erythromycin and 15 μg of SnCl₂·2H₂O at pH 4 for 15 min. ^99m Tc-erythromycin complex was stable for 6 h. Biodistribution studies in Albino mice bearing septic and aseptic inflammation models showed that ^99m Tc-erythromycin does not allow differentiation between septic (Staphylococcus aureus) and aseptic inflammation. The maximum accumulation of ^99m Tc-erythromycin at the infection site was observed in 30 min after administration and was followed by gradual decline. The abscess-tomuscle ratio for ^99m Tc-erythromycin was 5 ± 0.6, whereas that for the commercially available ^99m Tc ciprofloxacin was 3.8 ± 0.8.     

Synthesis and biodistribution of 99m Tc-PyDA as a potential marker for tumor hypoxia imaging

The ^99m Tc-pyrimidine-4,5-diamine (^99m Tc-PyDA) complex was prepared. The yield under the optimum conditions (5 mg of PyDA, pH 8, 25 μg of SnCl₂·2H₂O) was 96 ± 3%. The complex is stable in vitro for 24 h. The complex was tested on mice as potential marker for tumor hypoxia imaging. The complex showed high tumor hypoxia uptake with the target/nontarget (T/NT) ratio as high as ～3.     

Synthesis and evaluation of 99m Tc-NIDA and 99m Tc-DMIDA complexes for hepatobiliary imaging

1-Naphthylcarbamoylmethyliminodiacetic acid (NIDA) and diphenylmethylcarbamoylmethyliminodiacetic acid (DMIDA) were synthesized, characterized, and labeled with ^99m Tc using SnCl₂ as reducing agent. The parameters affecting the yield of ^99m Tc-NIDA and ^99m Tc-DMIDA were studied in detail. The optimum conditions ensuring high yield of ^99m Tc-NIDA (94.2 ± 2%) and ^99m Tc-DMIDA (93.1 ± 2%) are as follows: 30 mg of NIDA or DMIDA, 0.3 mg of SnCl₂·H₂O, pH 6, 15 min. The biodistribution in mice injected with ^99m Tc-NIDA and ^99m Tc-DMIDA showed high liver uptake at 10 min post injection, with fast biliary excretion. Accumulation of the activity in kidneys was negligible, especially after a long time post injection. Both ^99m Tc-NIDA and ^99m Tc-DMIDA can be applied as hepatobiliary imaging agents for the evaluation of the functional status of the hepatocytes and the patency of the biliary duct.     

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.     

Optimization of labeling conditions and bioevalution of 99m Tc-Meloxicam for inflammation imaging

Labeling of Meloxicam with ^99m Tc was done by direct addition of pertechnetate in isotonic solution to Sn-Meloxicam solution. High labeling yield (98%) was attained in 30 min at room temperature. The effect of various factors on the labeling yield was studied. No less than 0.5 mg of Meloxicam should be used to prevent the formation of colloids in the reaction medium. 75 μg of stannous chloride dihydrate was found to be sufficient to reduce all pertechnetate without the detection of free pertechnetate or colloids in the reaction mixture. The labeling should be done in alkaline solutions (pH 9–11). The labeled compound was separated and purified by HPLC. The biological distribution in infected mice demonstrates the suitability of ^99m Tc-labeled Meloxicam for inflammation and tumor imaging.     

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.     

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.     

Use of99m Tc as an energy standard for electron spectroscopy: promise and limitations

An electrostatic spectrometer was used to study the dependence of the position of theM ₅ line of conversion electrons from the 2.17-keV transition in⁹⁹Tc on the source thickness, in samples of different chemical compounds of Tc: metallic technetium, technetium dioxide, and pertechnate. Recommendations are given concerning the use of a source in the form of a film of metallic technetium (less than 10⁻⁷ g/cm² thick) on a platinum substrate for calibrating electron spectrometers in the energy range of a few kiloelectron volts. A procedure is described for preparing films of metallic technetium. Translated from Izmeritel'naya Tekhnika, No. 8, pp. 66–68, August, 1997.     

Synthesis and properties of 99Tc(I) and 99m Tc(I) hexacarbonyl in aqueous solutions

A procedure was developed for preparing Tc(CO)₆ClO₄ by carbonylation of a solution of technetium(I) tricarbonyltriaqua complex in 2 M HClO₄ in a pressure vessel at 100–170°C and CO pressure of 150 atm. The hexacarbonyltechnetium cation in solution was characterized by IR and ⁹⁹Tc NMR spectroscopy, and also by high-performance liquid chromatography (HPLC). The effect of particular acid and of synthesis conditions on the yield of the hexacarbonyltechnetium cation was examined, and the stability of this cation in aqueous solutions was evaluated. Conditions were found for preparing an aqueous solution containing ^99m Tc(CO) ₆ ⁺ .     

Technetium-99m Labeling of Antineoplaston A10 and Its Bioevaluation as a Potential Tumor Imaging Agent

Radiochemistry - Antineoplastons (ANPs) are compounds that have antitumor activities. ANPA10 was labeled with technetium-99m using stannous chloride as a reducing agent with the labeling yield of...     

Labeling of omeprazole with technetium-99m for diagnosis of stomach

Omeprazole, a proton pump inhibitor, was labeled with ^99m Tc to obtain ^99m Tc-omeprazole in ～96% yield in basic media. The optimum conditions were as follows: pH 9, 50 μg of SnCl₂·2H₂O, 30 min, and 3 mg of the substrate. ^99m Tc-omeprazole was stable for 6 h. Intravenous biodistribution of ^99m Tc-omeprazole showed that it concentrated in the stomach ulcer to reach about 22% of the total injected dose at 1 h post injection. This concentration of ^99m Tc-omeprazole in stomach ulcer may be sufficient for ulcer imaging.     

Preparation and preclinical evaluation of radioiodinated secnidazole as a possible tumor imaging agent

To develop a radiopharmaceutical localizing in tumor hypoxic tissues, secnidazole (SECN) was labeled with ¹²⁵I. The labeled product was prepared with the radiochemical yield higher than 96% when performing the reaction at 45°C for 30 min. The electrophilic radioiodination of SECN was done using different oxidizing agents. Iodogen appeared to be more effective than chloramine-T (CAT) and N-bromosuccinimide (NBS). ¹²⁵I-SECN was tested in vivo with a tumor model prepared by the intramuscular injection of Ehrlich cell line into the thigh muscle of mice. ¹²⁵I-SECN showed high accumulation in tumor hypoxic tissue (3.6% of injected dose per gram of organ at 2 h post injection). The target/nontarget (T/NT) ratio was high (T/NT = 6 at 24 h post injection). Thus, radioiodinated SECN shows promise as a selective imaging agent for diagnosis of tumor hypoxia.     

Coregistration of diffuse optical spectroscopy and magnetic resonance imaging in a rat tumor model

We report coregistration of near-infrared diffuse optical spectroscopy (DOS) and magnetic resonance imaging (MRI) for the study of animal model tumors. A combined broadband steady-state and frequency-domain apparatus was used to determine tissue oxyhemoglobin, deoxyhemoglobin, and water concentration locally in tumors. Simultaneous MRI coregistration provided structural (T2-weighted) and contrast-enhanced images of the tumor that were correlated with the optical measurements. By use of Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, showing precisely which tissue structure was probed optically. DOS and MRI coregistration measurements were performed on seven rats over 20 days and were separated into three tumor tissue classifications: viable, edematous, and necrotic. A ratio of water concentration to total hemoglobin concentration, as measured optically, was performed for each tissue type and showed values for edematous tissue to be greater than viable tissue (1.2 +/- 0.49 M/microM versus 0.48 +/- 0.15 M/microM). Tissue hemoglobin oxygen saturation (StO2) also showed a large variation between tissue types: viable tissue had an optically measured StO2 value of 61 +/- 5%, whereas StO2 determined for necrotic tissue was 43 +/- 6%.     

Synthesis and ultrastructure of plate-like apatite single crystals as a model for tooth enamel

Hydroxyapatite (HAp) is an inorganic constituent compound of human bones and teeth, with superior biocompatibility and bioactivity characteristics. Its crystal structure is hexagonal, characterized by a(b)- and c-planes. In vertebrate long bones, HAp crystals have a c-axis orientation, while in tooth enamel, they have an a(b)-axis orientation. Many methods can be used to synthesize c-axis oriented HAp single crystals; however, to the best of our knowledge, there have been no reports on a synthesis method for a(b)-axis oriented HAp single crystals. In this study, we successfully synthesized plate-like HAp crystals at the air–liquid interface of a starting solution via an enzyme reaction of urea with urease. Crystal phase analysis and ultrastructure observations were carried out, and the results indicated that the particles were single crystals, with almost the same a(b)-axis orientation as tooth enamel. It is hoped that by utilizing their unique surface charge and atomic arrangement, the resulting particles can be used as a high-performance biomaterial, capable of adsorbing bio-related substances and a model for tooth enamel.     

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.     

Development of an automated unit for extraction-chromatographic separation of the 99Mo/99m Tc generator couple

The design and automatic control scheme were developed for an extraction-chromatographic unit for producing ^99m Tc preparations. The unit is intended for operation under the conditions of medical radiological laboratories. Technical trials showed that the mean time of preparation of sodium [^99m Tc]pertechnetate radiopharmaceutical did not exceed 25 min.     

Labeling and biological evaluation of 99m Tc-azithromycin for infective inflammation diagnosis

Azithromycin, an antibiotic used to treat bacterial infections, was labeled with ^99m Tc. The maximum radiochemical yield of ^99m Tc-azithromycin, 97.5 ± 0.9%, was attained under the following conditions: addition of ^99m Tc to 2 mg of azithromycin in the presence of 50 μg of SnCl₂·2H₂O at pH 4, reaction time 30 min. ^99m Tc-azithromycin complex was stable for 6 h. Biological distribution of ^99m Tc-azithromycin was studied in mice infected with Staphylococcus aureus in the left thigh. The ratio of ^99mTc-azithromycin uptake in the bacterially infected and contralateral thighs, T/NT, for was found to be 6.20 ± 0.12 at 2 h after intravenous injection (higher than the ratio obtained with the commercially available ^99m Tc-ciprofloxacin), which was followed by gradual decline. The results obtained show that ^99m Tc-azithromycin can be used for infection imaging and allows differentiation between bacterial infection and sterile inflammation.     

Synthesis and Preliminary Biological Evaluation of 99mTc Tricarbonyl Ropinirole as a Potential Brain Imaging Agent

Ropinirole, a non-ergoline dopamine agonist, was labeled with ^99mTc tricarbonyl {[^99mTc(CO)₃·(H₂O)₃]⁺} with the aim of obtaining a new brain imaging agent. For in vivo use, the radiosynthesis of ^99mTc tricarbonyl ropinirole was performed by heating a solution containing ropinirole and the precursor, ^99mTc tricarbonyl, on a boiling water bath for 30 min. The influence of the substrate amount and pH on the reaction was studied to optimize the synthesis. The biodistribution and scintigraphic studies demonstrate the suitability of ^99mTc tricarbonyl ropinirole as a novel tracer for brain tumor imaging.

     

Labeling of tannic acid with technetium-99m for diagnosis of stomach ulcer

A procedure was developed for labeling tannic acid with ^99m Tc. The following conditions are required to achieve 95.5% yield of ^99m Tc-tannic acid: 150 μg of SnCl₂·2H₂O, 50 μg of the substrate, 30 min, pH 7. ^99m Tc-tannic was stable for 6 h. Experiments on biodistribution of orally administered ^99m Tc-tannic acid showed that it is concentrated in the stomach ulcer (50% of the total administrated dose at 1 h post administration). This concentration of ^99m Tc-tannic acid in stomach ulcer may be sufficient for ulcer radioimaging.     

Synthesis and characterization of a {ReO}3+ complex with S- and N-donor ligands and of its 99m Tc analog

A novel mixed-ligand ^99m Tc complex with mercaptobenzothiazole (mer) as ligand and aminothiazole (amino) as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using ^99m Tc-gluconate as precursor and a coligand/ligand ratio of 5. Under these conditions, the labeling yield was over 97% and the major product with radiochemical purity >97% was isolated by HPLC and used for biological evaluation. The reaction of [ReO(Citrate)₂]^? with mer and amino in hot MeOH yields [ReO(mer)(amino)OH(H₂O)₂]. The DFT study demonstrated that the complex contains distorted octahedral ReO(V). The Re coordination sphere consists of the terminal oxo group, the S donor atom of the deprotonated mer, the N atom of the deprotonated amino, OH group, and two water molecules. Biodistribution in mice demonstrated early brain uptake, fast blood clearance, and excretion through hepatobiliary system. Although the brain/blood ratio increased significantly with time, the novel ^99m Tc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.