Development and validation of an alternative procedure for quantitative quality control analysis of 99mTc-radiopharmaceuticals using a Geiger Müller counter.

BACKGROUND AND OBJECTIVES: In a hospital radiopharmacy with 2a operational level, including the preparation of radiopharmaceuticals from prepared and approved reagent kits, it is common to have a single activimeter or dose calibrator for labeling and fractionation, and to perform the quality controls of the 99mTc-radiopharmaceuticals. In certain cases, the accumulation of radioactive material or accidental contamination of the work area causes the background to exceed the limits to carry out the radiochemical purity analyses and it is necessary to look for viable alternatives. In this work, a Geiger Müller detector (equipped with a probe for measuring surface contamination) frequently used for radioprotection purposes, was validated as an alternative and its performance was compared against the activimeter for 99mTc-radiopharmaceuticals. MATERIALS AND METHODS: Using [99mTc]pertechnetate, systematic studies of error analyses and detector response to activity concentration, activity and measurement time were carried out in liquid matrices and in paper. The results were compared against an activimeter calibrated for [99mTc]Tc. RESULTS: The developed method was used to determine the radiochemical purity of the compounds [99mTc]Tc-MDP and [99mTc]Tc-MIBI by ascending paper chromatography tests, obtaining comparable values to those measured with an activimeter in the same system (within 1% uncertainty) and using the method of vial partitioning in a dedicated equipment. CONCLUSIONS: This work demonstrates that a Geiger Müller detector with a probe for measuring surface contamination can be adequately used to replace other equipment in the control of radiochemical purity in the hospital radiopharmacy.

Redox-Based Electrochemical Affinity Sensor for Detection of Aqueous Pertechnetate Anion.

Rapid, selective, and in situ detection of pertechnetate (TcO4-) in multicomponent matrices consisting of interfering anions such as the ubiquitous NO3- and Cl- or the isostructural CrO42- is challenging. Present sensors lack the selectivities to exclude these interferences or the sensitivities to meet detection limits that are lower than the drinking water standards across the globe. This work presents an affinity-based electrochemical sensor for TcO4- detection that relies on selective reductive precipitation of aqueous TcO4- induced by a 1,4-benzenedimethanethiol capture probe immobilized on an electrode platform. This results in a direct decrease in the electron transfer current, the magnitude of the decrease being proportional to the amount of TcO4- added. Using this approach, a detection limit of 1 × 10-10 M was achieved, which is lower than the drinking water standard of 5.2 × 10-10 M set by United States Environmental Protection Agency. The proposed approach shows selectivity to the TcO4- anion, allowing detection of TcO4- from a multicomponent groundwater sample obtained from a well at the Hanford site in Washington (well 299-W19-36) that also contained NO3-, Cl-, and CrO42-, without discernably affecting the detection limits.

Investigation of flow dynamics of wastewater in a pilot-scale constructed wetland using radiotracer technique.

Constructed wetlands (CWs) are used for the treatment of wastewater by natural processes. Knowledge of the flow dynamics of wastewater through the CWs is required to evaluate their performance, operation and design. The residence time distribution (RTD) approach was used to evaluate the above-mentioned parameters in a CW. The RTD of wastewater flowing through a pilot-scale CW was measured using Technetium-99 m (99mTc) as a radiotracer. The measured data were analyzed, and mean residence time and stagnant volumes were quantified under different operating conditions. A plug flow component in series along with a tank-in-series model with an exchange between the active and dead zones was used to simulate the measured RTD curves and investigate the flow dynamics of the flowing wastewater. The results of the study showed that the optimum flow rate and wastewater level in the CW was 2.3 m3/s and 0.6 m, respectively. Moreover, the results of the study will help in the operation and design of the existing wetland and design of new wetlands.

Highly Selective Colorimetric and Luminescence Response of a Square-Planar Platinum(II) Terpyridyl Complex to Aqueous TcO4(-).

Molecular recognition of an aqueous pertechnetate (TcO4(-)) anion is fundamentally challenging partly due to the charge-diffuse nature of this anion, which hampers design of new technologies for its separation and detection. To address this gap, simple salts of transition metal complexes that undergo a distinct spectroscopic change upon exposure to aqueous anions were explored. The Pt(II) complex [Pt(tpy)Br]SbF6 (tpy = 2,2';6',2″-terpyridine) undergoes a dramatic color change and intense luminescence response upon TcO4(-) uptake due to concomitant enhancement of Pt···Pt interactions. The spectroscopic response was highly selective and quantitative for aqueous TcO4(-) among other competing anions. Complementary Raman spectroscopy and microscopy techniques, structural determination, and theoretical methods were employed to elucidate the mechanism of this response at the molecular level.

Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [(99m)Tc(MIBI)6].

Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [(99m)Tc(MIBI)6]⁺ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [(99m)Tc(MIBI)6]⁺ since impurities such as (99m)Tc-reduced-hydrolyzed (RH), (99m)TcO(4)(-) and [(99m)Tc(cysteine)2]⁻ complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

Monitoring Tc dynamics in a bioreduced sediment: an investigation with gamma camera imaging of (99m)Tc-pertechnetate and (99m)Tc-DTPA.

We demonstrate the utility of nuclear medical imaging technologies and a readily available radiotracer, [(99m)Tc]TcO(4)(-), for the noninvasive monitoring of Fe(II) production in acetate-stimulated sediments from Old Rifle, CO, USA. Microcosms consisting of sediment in artificial groundwater media amended with acetate were probed by repeated injection of radiotracer over three weeks. Gamma camera imaging was used to noninvasively quantify the rate and extent of [(99m)Tc]TcO(4)(-) partitioning from solution to sediment. Aqueous Fe(II) and sediment-associated Fe(II) were also measured and correlated with the observed tracer behavior. For each injection of tracer, curves of (99m)Tc concentration in solution vs time were fitted to an analytic function that accounts for both the observed rate of sedimentation as well as the rate of (99m)Tc association with the sediment. The rate and extent of (99m)Tc association with the biostimulated sediment correlated well with the production of Fe(II), and a mechanism of [(99m)Tc]TcO(4)(-) reduction via reaction with surface-bound Fe(II) to form an immobile Tc(IV) species was inferred. After three weeks of bioreduction, a subset of microcosms was aerated in order to reoxidize the Fe(II) to Fe(III), which also destroyed the affinity of the [(99m)Tc]TcO(4)(-) for the sediments. However, within 3 days postoxidation, the rate of Tc(VII) reduction was faster than immediately before oxidation implying a rapid return to more extensive bioreduction. Furthermore, aeration soon after a tracer injection showed that sediment-bound Tc(IV) is rapidly resolubilized to Tc(VII). In contrast to the [(99m)Tc]TcO(4)(-), a second commercially available tracer, (99m)Tc-DTPA (diethylenetriaminepentaacetic acid), had minimal association with sediment in both controls and biostimulated sediments. These experiments show the promise of [(99m)Tc]TcO(4)(-) and (99m)Tc-DTPA as noninvasive imaging probes for a redox-sensitive radiotracer and a conservative flow tracer, respectively.

[Evaluation of the performance of transfer devices in a closed system using a radioactive solution of [(99m)Tc]]. / Évaluation de la performance de dispositifs de transfert en système clos au moyen d'une solution radioactive de [(99m)Tc].

INTRODUCTION: The exposure of workers to antineoplastic agents is potentially dangerous in the long term because of the teratogenic, carcinogenic and mutagenic hazardous of these products. These risks could be reduced by individual and collective shield measures. It's recommended to use transfer devices in a closed system for preparation of chemotherapy. METHOD: The aim of the survey is to analyse for five devices (four devices in a closed system transfer and a needle equipped with an air intake), the following criteria: transfer performance of a solution of a vial to another one, no leakage of the device and practicality in the use. A method implementing a radioactive solution of sodium pertechnetate [(99m)Tc] is used. RESULTS: Teva(®) and Cardinal(®) devices seem to be more efficient according to the ability to transfer one solution from a vial to another one with a low dead volume and low-level contamination in the around of the manipulation area. The Hospira(®) device appears an intermediate solution, while the Phaseal(®) device may be irrelevant for the transfer of a solution. DISCUSSION-CONCLUSION: Our study could attest that the methodology is simple to implement and cheap to compare devices on multiple selection criteria. This evaluation method is interesting because it allows a classification according to several criteria weighted according to the type of intended use. In addition to economic issues and protection of the worker, the use of such devices should be extended to other areas as the preparation of chemotherapy such as preparation of radiopharmaceuticals drugs.

¹¹¹Indium-labeled ultrafine carbon particles; a novel aerosol for pulmonary deposition and retention studies.

Continuous environmental or occupational exposure to airborne particulate pollution is believed to be a major hazard for human health. A technique to characterize their deposition and clearance from the lungs is fundamental to understand the underlying mechanisms behind their negative health effects. In this work, we describe a method for production and follow up of ultrafine carbon particles labeled with radioactive ¹¹¹Indium (¹¹¹In). The physicochemical and biological properties of the aerosol are described in terms of particle size and concentration, agglomeration rate, chemical bonding stability, and human lung deposition and retention. Preliminary in vivo data from a healthy human pilot exposure and 1-week follow up of the aerosol is presented. More than 98% of the generated aerosol was labeled with Indium and with particle sizes log normally distributed around 79 nm count median diameter. The aerosol showed good generation reproducibility and chemical stability, about 5% leaching 7 days after generation. During human inhalation, the particles were deposited in the alveolar space, with no central airways involvement. Seven days after exposure, the cumulative activity retention was 95.3%. Activity leaching tests from blood and urine samples confirmed that the observed clearance was explained by unbound activity, suggesting that there was no significant elimination of ultrafine particles. Compared to previously presented methods based on Technegas, ¹¹¹In-labelled ultrafine carbon particles allow for extended follow-up assessments of particulate pollution retention in healthy and diseased lungs.

Optimization of 99Mo measurement in 99mTc eluate samples using a scintillation detection system.

During elution of 99Mo-99mTc generators used in nuclear medicine, 99Mo might be extracted becoming a radionuclidic impurity. According to the International Atomic Energy Agency, the activity ratio between 99Mo and 99mTc in the eluate, at the moment of administration to the patient, should not exceed 0.015%. The aim of this work is to optimize a methodology to determine 99Mo activity in 99mTc eluates. Efficiency curves were obtained using a NaI(Tl)8"×4" scintillation detector. The methodology was validated by measuring a standard solution of 99Mo. It was concluded that the technique is sensitive to detect 99Mo in 99mTc eluates at levels below international limits.

Molecular recognition of pertechnetate and perrhenate.

This tutorial review covers the chemistry of artificial receptors designed to recognize the pertechnetate and perrhenate anions. It focuses on the molecular features that give rise to effective and selective complexation. Specific receptor classes are discussed in the context of available solution-phase and solid-state data with differences between pertechnetate and perrhenate binding behavior being highlighted where appropriate.

Assessment of multiple intravenous pumps infusing into a single site.

Much research has examined drug concentration and flow rates for a single intravenous pump infusing into a single site, but there is no information on the delivery of medications when a multiple-pump system is required. The intent of this study was to evaluate the accuracy of multiple-pump systems infusing into a single site. We noted large fluctuations when multiple intravenous pumps infused into a single site.

Adsorption of (99m)Tc-radiopharmaceuticals onto injection vials and syringes.

UNLABELLED: Many groups have reported the adsorption or retention of (99m)Tc-radiopharmaceuticals on injection vials and disposable plastic syringes. Such an enormously high loss of radioactivity would result in poor images, radiation exposure, waste, and economic burdens. We therefore decided to investigate the extent of adsorption or retention of several (99m)Tc-radiopharmaceuticals on injection vials, rubber stoppers, and plastic syringes. These radiopharmaceuticals are produced as lyophilized kits in our department and supplied to various hospitals practicing nuclear medicine in Pakistan. METHODS: A vial containing lyophilized material was reconstituted with 3 mL of freshly eluted Na(99m)TcO(4). A 1-mL aliquot of the resulting solution was withdrawn into a syringe at 0.25, 0.5, 1, 3, and 5 h after preparation. All preparations were stored at room temperature ( approximately 22 degrees C). After each withdrawal, the vial was reweighed and the activity remaining in the vial was measured using a radioisotope calibrator. The sample was reinjected into the vial. From the original weight and activity of solution in the vial, the initial activity per gram was calculated. From the weight and activity remaining in the vial after withdrawal of the sample, the activity per gram of the sample was calculated. From the difference between the initial activity per gram and the activity per gram of the sample, the percentage of (99m)Tc adsorbed on the vial was calculated. All preparations were kept in the syringe for 15 min, and the activity was measured before and after the syringe was emptied. The needle and plunger of the syringe were separated, and activity in the needle and plunger was also measured. RESULTS: The labeling efficiency of all radiopharmaceuticals used during these studies was more than 95%. In most cases, the activity of (99m)Tc found on the rubber stopper was less than 1%. Adsorption of (99m)Tc onto vials increased gradually with storage time. Adsorption was minimal at the initial stages, whereas maximum retention was noted after 5 h. Nearly 5% adsorption of activity was observed after 5 h of storage time on vials of sestamibi, mercaptoacetyltriglycine, dextran, ciprofloxacin, and dimercaptosuccinic acid (III and V). Retention of activity on needles ranged from 1% to 2% for all preparations studied. Plungers did not show any significant retention of radioactivity; in most cases, retention was less than 0.5%. The maximum retention of radioactivity on plastic syringe bodies was more than 3% for sestamibi, dimercaptosuccinic acid, dextran, pyrophosphate, and phytate. CONCLUSION: The results revealed that losses of radioactivity from (99m)Tc-radiopharmaceuticals in these objects (glass vial, rubber stopper, plastic syringes, plungers, and needles) are not alarming in our setup.

Design considerations for incorporating sodium iodide symporter reporter gene imaging into prostate cancer gene therapy trials.

This study was done to aid in the design of a phase I gene therapy trial in patients with prostate cancer. We determined the dosimetric characteristics of our reporter gene system when coupled with intravenous administration of radioactive sodium pertechnetate (Na(99m) TcO(4)) and determined the feasibility of using human sodium iodide symporter (hNIS) as a reporter gene to study the dynamics of adenoviral transgene expression in a large animal tumor. A replication-competent Ad5-yCD/mutTK(SR39) rep-hNIS adenovirus was injected into the prostate gland of dogs for dosimetry purposes, and into a canine soft tissue sarcoma (STS) for imaging purposes. After resection of the prostate, the amount of (99m)TcO(4)() sequestered in the prostate was determined, the radiation dose absorbed by the prostate and nontarget critical organs was calculated, and hNIS reporter gene expression was imaged in the STS by single-photon emission computed tomography (SPECT). On the basis of the findings from 25 dogs, the amount of (99m)TcO (4)() sequestered in the prostate ranged from 13 to 276 muCi. Using the highest value observed, absorbed radiation dose to critical organs was calculated and found to be below U.S. Food and Drug Administration limits for diagnostic imaging. Also, (99m)TcO (4)() uptake was readily detected by SPECT and found to persist in vivo for at least 4 days. On the basis of our dosimetry calculations, up to five imaging procedures can be safely performed in humans after intraprostatic injection of the Ad5-yCD/mutTK(SR39)rep-hNIS adenovirus and the hNIS reporter gene system can be used to study the dynamics of adenoviral gene therapy vectors in large animal tumors.

Functionalized TiO2 nanoparticles for use for in situ anion immobilization.

Anatase particles (40-60 nm) were coated with an organosilane monolayer terminated with an ethylenediamine (EDA) ligand. These functionalized nanoparticles (FNPs) were then treated with an aqueous solution of Cu(II) to create a cationic Cu-EDA complex bound to the nanoparticle surface. Cu(II) and EDA ligand incorporation were confirmed by X-ray photoelectron spectroscopy (XPS) analysis. The Cu(EDA)2 FNP was then studied for its binding affinity for pertechnetate anion from a Hanford groundwater matrix. The Cu(EDA)2 FNP was also evaluated for its injectability into a porous medium for possible application as a subsurface semipermeable reactive barrier. Injection was readily accomplished, and resulted in a highly uniform distribution of the FNP sorbent in the test column.

[Development of the chromatography analysis of liquid trapping 99mTc-Technegas using Jikei impinger].

We developed the equipment which collected 99mTc-Technegas into liquid (saline) and named this equipment an impinger of Jikei University Style. We further developed a technique using this impinger to evaluate its formation qualitatively by paper chromatography. Utilizing this technique we investigated various factors that caused environmental contamination by 99mTc-Technegas, including changes over time in a Technegas generator. It was demonstrated that upon getting mixed with oxygen gas to the argon gas, the Technegas generator induced contamination of 99mTc-Pertechnegas easily, leading to changes in its formation. The change of formation quality of the Technegas generator with the lapse of time was also revealed. These findings indicated that the maintenance and inspection of the equipment were important. This method is a simple and easy technique for the evaluation of 99mTc-Technegas formation, making it possible to perform the quality control of examination agent and the Technegas generator.

Macrophage targeting with 99mTc-labelled J001 for scintigraphic assessment of experimental osteoarthritis in the rabbit.

The potential of scintigraphy with technetium 99m-labelled J001 (99mTc-J001) to detect synovitis was studied in 15 rabbits with osteoarthritis (OA) of the right knee (section of cruciate ligaments), in five sham-operated rabbits and in four non-operated rabbits. J001 is a non-pyrogenic, acylated poly (1,3) galactoside isolated from the membrane of a non-pathogenic strain of Klebsiella pneumoniae which is able to bind selectively to macrophages via the binding to CD11b and CD14 molecules. The results of 99mTc-J001 scintigraphy were compared with those of scintigraphy with 99mTc-labelled methylene diphosphonate (99mTc-MDP) and GC-APG (a derivative of J001 unable to bind macrophages in vitro). The mean scintigraphic ratios (diseased healthy knee) of 99mTc-J001 were significantly higher in OA rabbits than in sham- and non-operated rabbits, from as early as day 18 until day 90. 99mTc-J001 scintigraphy demonstrated earlier increased uptake than 99mTc-MDP scintigraphy. The mean scintigraphic ratios of 99mTc-J001 were significantly higher than those of 99mTc-GC-APG (which remained normal) in OA rabbits. The normal scintigraphic ratios of 99mTc-J001 in sham-operated and non-operated rabbits, as well as of 99mTc-GC-APG in OA rabbits, suggested that the increased uptake demonstrated with 99mTc-J001 in OA rabbits, as early as day 18 corresponded to imaging of synovitis via elective macrophage targeting. These results showed that 99mTc-J001 scintigraphy should be a specific method of detecting synovitis in OA.

[Simplified analytical method of 99mTc-labeled phosphonate].

A simplified and rapid analytical method of 99mTc-labeled phosphonates was tested using a mini-column based on an anion-exchange type of cartridge. Free 99mTcO4- in the prepared solutions of 99mTc-labeled phosphonate was eluted from the column by a neutral phosphate buffer solution. Partly components of the 99mTc-labeled phosphonates was eluted from the column by a 100 mM sodium phosphonate solution, while the residual components were not eluted from the mini-column. In addition, for analysis of 99mTc-labeling rate in 99mTc-MDP solution, this method requires much less time than thin layer chromatography (TLC). Therefore, the method is more suitable for analysis of 99mTc-labeled phosphonates than TLC now in use, particularly rapid analysis for 99mTc-labeling rate of the compounds and the stability.

A rapid chromatographic method for quality control of technetium-99m-bicisate.

UNLABELLED: The purpose of this work was to develop a simple and rapid method to determine the radiochemical purity of 99mTc-bicisate. METHODS: A rapid paper chromatographic (PC) method was developed to determine the radiochemical purity of 99mTc-bicisate and compare the results with those of the manufacturer's recommended method. The present PC method included Whatman 3MM paper as the solid phase and ethyl acetate as the solvent. RESULTS: The time for chromatography by this technique was 4-5 min compared to about 23 min by the manufacturer's method. The Rf value of 99mTc-bicisate (Rf = 0.9-1.0) was widely different from those of 99mTcO4- and reduced 99mTc (Rf = 0.0 for both) so the chromatographic strip after development could be readily cut into two segments, in order to determine the labeling yield. CONCLUSION: No significant difference in labeling yields was found between the present method and the manufacturer's method. The PC method using Whatman 3MM paper and ethyl acetate is a simple and fast technique to determine the radiochemical purity of 99mTc-bicisate and may be substituted for the manufacturer's recommended method to save time.