Labelling and quality control of gentamycin with99mTc and biodistribution

Gentamycin sulfate (antibiotic) was labelled with^99mTc with high radioactive yield. Technetium species were studied using different types of sephadex on columns. Stannous chloride was used as reducing agent for heptavalent^99mTc obtained directly from generator to lower oxidation state prior to labelling. Optimal pH was found to form the most stable complex. A lyophilized kit was prepared and it was stable for more than three months. Mice, rats and rabbits have been used as exprimental animals. Accumulation of more than 20% of the labelled formula in kidneys 30 minutes post injection in rats has been found. Gamma camera images in rabbit were clear enough for kidney delineation thirty minutes after injection.     

Standardization of quality control methods for99mTc radiopharmaceuticals

Physico-chemical characterization of^99mTc-radiopharmaceuticals is presented. Limiting pH values, iso-osmotic pressure and the apparent coefficient values between two immiscible phases are determined too. A selection of radiochromatographic methods /stationary or mobile phase/ for routine quality control of^99mTc radiopharmaceuticals for radiochemical purity was made. The methods chosen are simple, accurate, sufficiently sensitive and fast in operation. The mean values were determined for^99mTc radiopharmaceutical distribution per organs, characteristic for the tested preparates and for radiochemical purity, as well as the time interval from injection to sacrifice of the animals.     

Labelling of human serum albumin millimicrospheres (hamm) with99mTc

Human serum albumin microspheres were labelled with^99mTc as a single step kit with radiochemical yields higher than 95%. With respect to the organ distribution in mice, the per cent of injected dose in liver was 78%.     

Comparative study of quality control procedures for99mTc radiopharmaceuticals

Paper and TLC chromatographic methods have been evaluated for the control of the labeling and stability of eight Tc-radiopharmaceuticals. The different supporting media and eluents have been studied and the most suitable methods have been classified according to their usefulness, reliability and rapidity. Moreover the artefacts encountered have been investigated. Alumina is found not suitable for its interference with TcO ₄ ^– . Acetate buffer seems to be labeled by TcHR inducing frequently subsequent smearings. Methyl ethyl ketone is optimal for the quantification of TcO ₄ ^– except in Tc-HIDA. TcHR never migrates as well as Tc-S Coll, Tc-MAA and Tc-HSA. The well-defined separation of TcO ₄ ^– and TcHR from the radiopharmaceutical often requires a two-step method.Throughout this paper, the symbol Tc will be used to represent technetium-99m.     

The quality of99mTc eluates

The possible effects of several protecting procedures on the quality of^99mTc eluates were investigated. The content of⁹⁹Mo in the eluates (⁹⁹Mo breakthrough) was expressed in (%) with respect to the total adsorbed⁹⁹Mo radioactivity and in () i.e. as the ratio of⁹⁹Mo and^99mTc radioactivities in each particular eluate. The radiochemical purity was expressed in (%) of^99mTc(VII) in the eluates. The content of Al³⁺ and Cu²⁺ as chemical impurities was also determined.     

Comparative quality control of some bone-seeking99mTc radiopharmaceuticals by gel chromatography

The radiochemical purity of the three osteopatic ligands:^99mTc(Sn)-PyP,^99mTc(Sn)-DPD and^99mTc(Sn)-MDP has been determined by gel chromatography on Sephadex. The results of the analyses strongly depend on the composition of the eluent. The dilution effect of pure saline as eluent was observed in all the preparations examined. The most sensitive was found to be^99mTc(Sn)-PyP. The retention of^99mTc activity bound to the gel matrix (^99mTc-hydrolyte) was over 30%. The diphosphonates were found to be more stable (retention 10–15%). The retention is substantially lower, i.e. a high recovery of the labeled complexes is obtained when the eluent contains the ligand. The best results are obtained when the eluent contains the same concentrations of ligand and reductant as in the labeled complex. There was no significant difference in the behavior of the given radiopharmaceuticals prepared as a fresh solution and in the freeze-dried kit.     

Chemical and biological evaluation of 99mTc (CO)3 and 99mTc complexes of some IDA derivatives

The confirmation that N-substituted imidodiacetic acids, as small and simple ligand systems containing amines and carboxylic acids, could be coordinated to the tricarbonyl core and form inert complexes with [^99mTc (CO)₃(H₂O)₃]⁺, is demonstrated. The HPLC quality control results of ^99mTc-carbonyl tagged IDA molecules, performed by gradient HPLC, have shown that HIDA, EHIDA and p-butyl-IDA form complexes with [^99mTc(CO)₃(H₂O)₃]⁺, with a labeling yield of ~90% for each of ^99mTc(CO)₃ IDA derivatives. However, the changes in the structure of labeled compounds, e.g., EHIDA, influence the changes in the biological behavior. In comparison with ^99mTc-EHIDA, the biliary excretion of ^99mTc(CO)₃ EHIDA was lower, but the urinary excretion higher. This revised version was published online in July 2006 with corrections to the Cover Date.     

Technetium-99m-diethyl-IDA instant kit: Labelling kinetics and biological properties

A formulation of stannous-diethyl-IDA freeze-dried kit, containing 50 mg diethyl-IDA and 0.4 mg hydrated stannous chloride, to be labelled with technetium has been developed for hepatobiliary scintigraphy. Gel chromatography column scanning technique has been applied for determination of technetium fractions in the preapration. The optimal pH value of the preparation with a high hepatobiliary specificity was found between 5.5 to 6.0. Effect of ligand to metal ratio on the stability of the prepared Sn-diethyl-IDA solution prior mixing with technetium has been investigated. The reaction conditions (initial pH) between the ligand and stannous ion affects the percent hydrolysis of the labelled compund, i.e. the formation rate of the complex. The organ distribution data of^99mTc-diethyl-IDA in mice for 60 minutes post injection were satisfactory. The radiopharmaceutical exhibits rapid blood clearance, great hepatic clearance and very short hepatocyte transit time. Uptake of the radiopharmaceutical in various organs of mouse at 5 minute post injection showed that the greater part of the injected radioactivity has distributed between liver and intestine. However, about 12% and 60% of the injected dose has been found in liver and intestine respectively. The renal uptake of the HB agent in mice is relatively low and decreases with time to become about 0.3% at 60 minutes post injection. Blood clearance data of the radiopharmaceutical kit in rabbits showed that the HB agent is-rapidly cleared, since the initial decrease was very fast with a half-time of 1.5 minutes.     

Determination of molybdenum in biological materials by combined extraction of99Mo and99mTc

Combined extraction of⁹⁹Mo and its daughter-product^99mTc enables a rapid determination of molybdenum in biological samples by neutron activation analysis. A procedure and its application to standard kale powder and standard animal blood are reported.     

Purity control of the radiopharmaceutical thiamine pyrophosphate-Sn-99mTc

A new purity control method was developed in order to assure the radiochemical purity of thiamine pyrophosphate-Sn-^99mTc. The method described consists in ascending cromatography using Whatman N^o 1 for support and 5% sodium citrate as solvent. It is capable of detecting free^99mTcO ₄ ^– and colloid formation, the most frequent impurities found in^99mTc radiopharmaceuticals.     

Synthesis of 99mTc(CO)3-NOET via [99mTc(OH2)3(CO)3]+ precursor and comparative biological studies with 99mTcN-noet

Summary The organometallic precursor fac-[^99mTc(CO)₃(H₂O)₃]⁺ was reacted with N-ethoxy, N-ethyl dithiocarbamate (NOET) in phosphate buffered saline (pH 7.4) at room temperature for 30 minutes to produce the ^99mTc(CO)₃-NOET complex. The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature (RT) was observed over a period of 6 hours. Its partition coefficient indicated that it was a lipophilic complex. The biodistribution comparison in mice of the ^99mTc(CO)₃-NOET complex and the ^99mTcN-NOET complex showed that the former had a lower heart and brain uptake as compared to that of the latter, suggesting the incorporation of the [^99mTc(CO)₃]⁺ core into the NOET ligand does not improve the biological features as a myocardial imaging agent.     

Preparation of salicylidene-aminates labeled with99mTc

A series of bidentate and tetradentate ligands with azomethine and Ar–OH functional groups derived from salicylaldehyde and primary alkyl or aryl monoamines and diamines has been synthesized and labeled with^99mTc at various pH's using stannous chloride as reducing agent. The labeling efficiency was monitored by thin layer and paper chromatography.     

Quality control and clinical application of two bone imaging99mTc radiopharmaceuticals

The radiochemical purity of MDP and HEDP has been determined by means of gel chromatography on Sephadex and thin layer chromatography on plastic foil silica gel. The comparison of the two radiopharmaceuticals shows equal level of complex formation with^99mTc. The biodistribution demonstrated that the application of HEDP allows earlier scanning than MDP. MDP and HEDP show equal effectivity during the clinical investigations. There is no significant difference in the radiochemical purity within six hours after the reconstitution of the freeze-dried kits. HEDP kit demonstrates shorter period of accumulation and equivalent complex formation levels, so it can be used in routine nuclear medicine diagnostics together with MDP kit.     

99mTc generator with hydrated MnO2 as adsorbent of 99Mo

An ^99mTc generator with MnO₂ as adsorbent of ⁹⁹Mo was investigated. Through batch experiments the retention of ⁹⁹Mo onto MnO₂was studied as a function of the shaking time and the pH value of the ⁹⁹Mo solution. It was found that ⁹⁹Mo showed a retention of 100% onto MnO₂ at the pH range from 3 to 11, and the equilibrium distribution was reached in less than 10 minutes. In column experiments the retention of ⁹⁹Mo onto MnO₂ was also high: 99.72%. In this case, the pH of the utilized ⁹⁹Mo solution was 5. The ^99mTc could be eluted from the MnO₂-⁹⁹Mo column by using either distilled water with a pH of 5 or an aqueous solution of 0.9% NaCl. With the saline solution, the ^99mTc elution yields were higher than 80%, and only one aliquot of 5 ml was needed to get these yields. The best results were obtained when the column was packed with 1 g of MnO₂. The water and the saline solution were passed through the column at a rate of 1.25 ml/min.     

Labeling of scorpion venom with 99mTc and its biodistribution

Labeling of scorpion venom (SV) was successfully achieved with ^99mTc using direct chelating method. Venom was labeled with ^99mTc using stannous chloride as reducing agent. Preliminary studies were done to establish the optimum conditions for obtaining the highest yield of the labeled venom. The labeling technique is effective, as a maximum labeling yield (97 %) was obtained after 30-min reaction time by using 80 μg SV in phosphate buffer of pH 7 and 25 μg Sncl₂·2H₂O at room temperature. Venom was injected into normal mice to determine the excretion pathway. Biodistribution studies in normal mice with SV shows rapid clearance of the venom from blood and tissue except for kidneys. The improvement of the immunotherapeutic treatment of envenomation requires a better knowledge of the biological actions of the SV since tissue distribution studies are very important for clinical purpose.