Radiochemical Purity Values Research Articles

Automating the production of [Fe18FF2(BnMe2-tacn)] and investigating radiostabilisers for use with high-activity [18F]F−

Abstract The manual radiofluorination and purification of [FeF3(BnMe2-tacn)] (tacn = 1,4,7-triazacyclononane) using 18F− in aqueous EtOH has been translated to a GE FASTLab™ automatic synthesis platform and optimised by conducting a series of low-activity radiolabelling experiments to explore the effects of varying the precursor concentration, temperature, heating time, addition of NaOAc buffer and EtOH:H2O ratio. The optimal conditions were determined to be 1 mg/mL of the precursor being heated at 120 °C for 10 min in 75 %:25 % EtOH:H2O containing 18F−, with elution using 10 mM NaOAc, giving 61 % radiochemical yield (RCY). These conditions were then employed with high-activity 18F− giving a 97 % radiochemical purity (RCP) at t = 0, which decreases by 22 % over 5 h. Sodium ascorbate, nicotinamide and p-benzoic acid (pABA) were then tested as potential radiostabilisers for this system, initially using low-activity 18F−. These experiments revealed very rapid defluorination of the radioproduct in the presence of sodium ascorbate. In contrast, both nicotinamide and pABA appear to be effective radiostabilisers, resulting in RCP values of 91 % and 89 %, respectively, after 2 h, which compare with an RCP of 81 % under analogous conditions at t = 2 h in their absence. High-activity experiments were then undertaken with addition of 5 mg/mL of nicotinamide, with a radio-active concentration (RAC) of 220 MBq/mL, giving RCY of 26 % and following purification, RCP values for the [Fe18FF2(BnMe2-tacn)] product of 97 % at t = 0 and 86 % after 3 h.

Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of [131I]Iodine-α-Mangostin for Breast Cancer Diagnosis and Therapy.

The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including -20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at -20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at -20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.

Features and Practical Aspects of Radiochemical Purity Determination of Receptor-Specific Lu-177 Radiopharmaceuticals as Exemplified by [<sup>177</sup>Lu]Lu–PSMA-617

Radiochemical purity (RCP) is one of the key quality criteria for radiopharmaceuticals (RPs) used in clinical practice. The results of RCP measurements depend on the analytical technique, as well as detection parameters, which are specific to a particular analytical system. When reviewing literature data on the synthesis, pharmaceutical development, preclinical and clinical trials of the same radiopharmaceutical by different authors, one may note significant variability in the RCP values obtained. Hence, it is important to carefully select analysis parameters and study their influence on the results. The aim of the study was to compare previously published and self-developed procedures for RCP analysis of 177 Lu-RPs in terms of their efficiency in the detection and quantification of possible radiochemical impurities, as well as to determine the analytical system parameters that have a significant impact on the interpretation of the analysis results, using [ 177 Lu]Lu–PSMA-617 as a case study. Materials and methods : the study used samples of [ 177 Lu]Lu–PSMA-617 with a volume activity of lutetium-177 of 150–4800 MBq/mL, containing 10–100 µmol/L of the PSMA-617 precursor and 30 mmol/L of sodium acetate as a buffering solution (pH 4.5). The samples were tested by high-performance liquid chromatography (HPLC) and thin-layer chromatography in the conditions described in the literature and developed in the course of the work. Results : the study showed a significant influence of the chosen analytical procedure on the results of [ 177 Lu]Lu–PSMA-617 RCP assessment. The profile of possible radiochemical impurities requires the use of high-resolution HPLC techniques. Conclusions : the analytical procedure developed and applied by the authors is quite effective. The results of RCP assessment are influenced by the detection system parameters, such as the length and inner diameter of the flow cell and the means of analytical signal processing (peak extraction parameters, smoothing parameters, and noise subtraction/suppression). This fact necessitates validation considering the characteristics of a particular analytical system and demonstrates the need to assess interlaboratory precision in the framework of the implementation and verification of analytical procedures.

Determination of Total Radiochemical Purity of [18F]FDG and [18F]FET by High-Performance Liquid Chromatography Avoiding TLC Method

The goal of this work was to present two high-performance liquid chromatography (HPLC) method that could be applied for the determination of the total radioactive purity of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET). The separation of [18F]fluoride ions, [18F]FET and [18F]FET intermediate was accomplished on LiChrosper RP-18, 250 × 4 mm, 5 µm (Merck) analytical column. For mobile phase 10 mM potassium dihydrogen phosphate buffer at pH7 (A) and acetonitrile (B) was used: 0–2 min: 15% B; 2–12 min: 85% B; 12–15 min: 15% B, respectively. Analysis of [18F]FDG was performed using LiChrosper 100 NH2, 250 × 4.5 mm, 5 µm (Merck) analytical column. The initial mobile phase composition was 10 mM KH2PO4 buffer (pH7) and acetonitrile (15:85, v/v) and the acetonitrile ratio was decreased to 15% at 2 min after the sample injection and held for 5 min. Complete elution of [18F]fluoride ions from stationary phases could be achieved by adding 10 mg/mL K[19F]F to radioactive samples in a ratio 1:1 during the sample preparation. Recovery of [18F]fluoride ions ranged from 99.5 to 100.6%. The validation of the developed methods showed good results for linearity (r2 = 0.9981–0.9996), specificity (RS = 3.7–10.2), repeatability (%Area RSD% = 1.2–4.3%) and limit of quantitation (LOQ = 1.6–4.5 kBq). During the cross-validation similar radiochemical purity values were obtained by the novel HPLC methods and thin layer chromatography performed according to the recommendations of the Ph. Eur. monographs.

A suitable time point for quantifying the radiochemical purity of 225Ac-labeled radiopharmaceuticals

BackgroundAs 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and QC testing. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately quantified.ResultsSix ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP for any pre-equilibrium measurement taken at an early time point. The 585 TLC measurements span RCP values of 1.8–99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. A measurement of RCP > 90% at 2 h predicts a true RCP > 97% and guarantees that RCP will exceed 90% after secular equilibrium is reached. These findings were independently validated using NaI(Tl) scintillation counting and high resolution gamma spectroscopy on a smaller set of samples with 10% ≤ RCP ≤ 100%.ConclusionsRCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC using various methods of quantifying particle emissions. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.

Physicochemical Properties Of 131I-Rutin Under Acidic Labeling Condition As A Radiolabeled Compound For The Diagnosis Of Cancer

Radiolabeled rutin (131I-rutin) has potential use in future diagnosis of cancer. The physicochemical characteristics of 131I-rutin are essential in regard to its distribution and accumulation in the body. Therefore, to ensure successful delivery of a labeled compound, it is necessary to evaluate its physicochemical properties. The labeling of 131I-rutin was accomplished using the oxidation method assisted by Chloramine-T under acidic conditions. Radiochemical purity value was measured by thin-layer chromatography (TLC-SG F254) using 100% methanol as the mobile phase. The electrical charge of 131I-rutin was determined by the paper electrophoresis. Moreover, the lipophilicity (P) was evaluated by the partition coefficient in the organic-water liquid. Plasma protein binding was determined in vitro by precipitation method using a 5% trichloroacetic acid (TCA) solution. The results showed that 131I-rutin has a neutral charge and a lipophilicity value (Log P) of 0.395 ± 0.203 (hydrophilic), and was bound to human blood plasma proteins with a percentage of 69.36% ± 1.88%.

Comparative Analysis of the Clinical Use of 99mTechnetium-Labeled Recombinant Target Molecules in Different Dosages for the Radionuclide Diagnosis of Her2-Positive Breast Cancer

Background. The chief goal in assessing the Her2/neu status in clinical practice is to identify indications for targeted therapy. The main methods for determining the Her2/neu status are an immunohistochemical method and fluorescence in situ hybridization (FISH); however, despite their widespread use, they have a number of significant disadvantages. Over the past few years, radionuclide diagnosis using a new class of alternative scaffold proteins that meet all the requirements for optimal radionuclide delivery to tumor cells has become widespread. Objective: comparative analysis of the effectiveness of radionuclide imaging of Her2-positive breast cancer using 99m technetium-labeled recombinant molecules in different dosages. Material and methods. The investigation enrolled 22 patients with breast cancer (T1-4N0-2M0) before systemic therapy: 11 had Her2/neu overexpression; 11 had no marker expression. The patients’ mean age was 50.7 ± 2.3 years. Morphological and immunohistochemical studies were performed in all cases. FISHanalysis was carried out in the presence of the Her2/neu 2+ value. The agent was prepared immediately before using in dosages of 500 and 1000 µg, after which it was slowly administered intravenously to the patient. Whole-body scintigraphy and chest single-photon emission computed tomography were conducted at 2, 4, 6 and 24 hours after administration. Results. The radiochemical yield and radiochemical purity values were 77 ± 9% and 99 ± 1%, respectively. The activity of the agent immediately before administration was 416 ± 135 MBq for the 500 µg group and 349 ± 133 MBq for 1000 µg group. Analysis of the findings indicated that the higher uptake of the agent by organs without tumor lesion was observed in the kidneys, liver, and lungs. The highest renal absorption of the agent was observed in both study groups (0.135 ± 0.042 and 0.191 ± 0.047 mGy, respectively). The effective dose was 0.009 ± 0.002 mGy for the 500 µg group and 0.010 ± 0.003 mGy for the 1000 µg group. The better distribution between the tumors with Her2/neu positive and negative statuses was observed 2 hours after administration in the 500 µg group with the mean tumor/background value of 37 ± 19 for Her2-positive tumors, and 5 ± 2 for Her2-negative tumors (p < 0.001). Conclusion. The findings suggest that the test radiopharmaceutical agent at a dose of 500 µg can be considered as a new additional method to diagnose Her2-positive breast tumors.

Study of the peak splitting in an alternative method for the radiochemical purity measurement of 99mTechnetium-sestamibi

One of the alternative methods for the measurement of radiochemical purity (RCP) of Technetium-sestamibi uses Whatman 3MM paper as the stationary phase and ethyl acetate as the mobile phase. However, alternative method shows peak splitting and shouldering of the radiopharmaceutical. This could be because of higher levels of analyte. We aimed to assess the effect of sample dilution (1 : 1) on this method and to compare these RCP values with the reference method. The diluted samples showed a unique peak in the radiopharmaceutical zone, but the RCP values were significantly different (P<0.05) and correlated poorly with the reference method.

Study to Define Frequency in Routine Analytical Controls in the Radiolabelling Process

In the radiolabelling process, the frequency of routine analytical testing must be defined with a risk assessment based on different factors (Pharmeuropa Vol. 26 No. 2, 5.19). Aim of this study is to define the criteria based on the risk assessment required for setting the frequency of analytical controls. 331 preparations of three different radiopharmaceuticals labeled with 99mTc were examined analyzing temporal trends of radiochemical purity values, potential correlation between radiochemical purity values and total radioactivity content of bulk as well as potential correlation between radiochemical purity values and radioactivity concentration of bulk. The analysis shows no direct correlation between percentage of radiochemical purity and total radioactivity content of preparation and between radiochemical purity values and radioactivity concentration in final bulk solution. Moreover, the routine analytical controls executed for one year on each preparation made it possible to determine how the analytical values do not have inter-operator dependency and there is no evidence of specific temporal trends over time. The study is aimed to assess any eventual criticality related with radiochemical purity tests, determine the possibility of a parametric release and the optimal frequency of tests, without reducing the level of safety of the preparations. This will produce a substantial reduction of costs and of radiation exposure to ionizing radiation of the staff dedicated to Quality Control procedures.

Particle-size and radiochemical purity evaluations of filtered 99mTc-sulfur colloid prepared with different heating times.

Sentinel node lymphoscintigraphy using colloidal particles has become common practice at many institutions. The ideal particle size for colloids such as filtered (99m)Tc-sulfur colloid ((99m)Tc-FSC) in sentinel node studies is 15-100 nm. It is reported that the use of a reduced heating time during the reconstitution process results in an increased number of smaller particles (<30 nm). However, it is unclear whether these smaller particles (>15 nm) would be of benefit in sentinel node studies. This study sought to better define particle size by using electron microscopy, as well as to evaluate the radiochemical purity (RCP) of (99m)Tc-FSC at various time points after filtration. One group of (99m)Tc-sulfur colloid ((99m)Tc-SC) preparations was reconstituted using the standard heating time of 5 min, and another group was prepared using a reduced heating time of 3 min. The (99m)Tc-SC preparations were passed through a 0.2-μm filter, and retained filter activity was measured. RCP values were collected at 0, 1, 3, and 6 h after filtration, and the particle sizes were measured at 0 and 6 h after filtration. Average RCP values (± SD) for (99m)Tc-FSC with 5-min heating were 98.4% ± 3.0% and 98.3% ± 1.8% for 0 h and 6 h, respectively (n = 6). Average RCP values for (99m)Tc-FSC with 3-min heating were 98.4% ± 4.1% and 96.9% ± 3.1% for 0 h and 6 h, respectively (n = 6). Electron microscopy data showed that median particle sizes for the 3-min heating at 0 and 6 h were 24 and 35 nm, respectively. Median particle sizes for the 5-min heating at 0 and 6 h were 29 and 27 nm, respectively. The proportion of particles within the ideal range for sentinel node lymphoscintigraphy was similar between the heating methods (91.1% for 3-min heating at 0 h and 88.8% for 5-min heating at 0 h, P = 0.1851). Our results indicate that although there are slight significant differences in RCP value, particle size, and particle number for (99m)Tc-FSC prepared using either a standard or a reduced heating time, both methods produce particles within the optimum range for sentinel node studies.

Evaluation of alternative rapid thin layer chromatography systems for quality control of technetium-99m radiopharmaceuticals

Whatman 3MM™ and Tec-Control™ systems were evaluated as ITLC-SG alternatives for 99mTc-radiopharmaceuticals. They compare well in accuracy and reproducibility, and are faster and more convenient than ITLC-SG. Tec-Control™ radiochemical purity values for 99mTc-sestamibi were more conservative than ITLC-SG. Full solvent migration was not reproduced for 99mTc-tetrofosmin in Tec-Control™, and for this Whatman 3MM™ is preferred. Developing times were 10–15min, 7–9min and ~1min for ITLC-SG, Whatman 3MM™ and Tec-Control™, respectively. Overall, Tec-Control™ strips are preferred due to speed and ease of use.

Abstract 2677: Comparison of different methods for radiochemical purity (RCP) control of 99mTc-tetrofosminin oncology.

Abstract Background : The 99mTc-tetrofosmin is a radiopharmaceutical used in oncology for scintigraphic quantification of the myocardial perfusion. The reference method for quality control is thin layer chromatography, using TLC SA bands. This method is simple but only separates two types of impurities: free technetium and hydrolyzed technetium combined to hydrophilic impurities such as gluconate-99mTc and takes from 30 to 35 minutes. Alternative methods by planar or liquid chromatography have been developed (Whatman® (W) plate, Sep-Pak® or HPLC). The aim of our study is to evaluate each method versus the reference one. Methods : The reference method is a method using planar chromatography TLC SA tape, size 1 cm x 20 cm. Two marks were scored: one at 3 cm from the bottom indicates the deposit (10 μL of the preparation) and the other at 15 cm from the bottom the end of migration. Mobile phase was acetone: dichloromethane (65:35, v/v). The band marks were quantified by radioactive counting using a miniGITA® radiochromatograph (Raytest) equipped with a scintillation probe. The other planar chromatographic methods are W 1 (0.18 mm) and W 3MM (0.34 mm), the principle and the quantifying method are similar to reference method. SEP-Pak®(Waters) method uses a C18 chromatography column with 2 mobile phases (NaCl 0.9% and ethanol) and a sample volume between 25 to 50 μL. Activity was quantify with a calibrator CRC 25® (Capintec) The chromatographic system consisted in a Symmetry Shield® column RP18 5μm 100Å (Waters) with a gamma detector Gammaram® (Lablogic). Empower® software (Waters) is used for peak integration. The mobile phase flowing at a rate of 1.0 mL / min consisted in a mixture of acetonitrile and Titrisol® buffer (Waters) (40:60, v/v), the sample volumes were no more than 10 to 30 μL. Results : The RCP was measured simultaneously by the different methods with 30 preparations. For HPLC, mean RCP = 97.21%, σ= 2.178% [91.6%-99.63%]. For TLC SA, mean RCP = 97.99%, σ= 1.135% [94.31%-99.86%]. For Sep-Pak® mean RCP = 97.15, σ= 1.133 [94.96%-99.55%], For W 3 MM mean RCP = 99.11 σ= 0.3252 [98.28%- 99.81%], For W 1 mean RCP = 98.32 σ= 0.5677 [97.01%-99.23%]. The results obtained by these methods were compared using the Wilcoxon t test.α = 0.05. The RCP obtained by TLC SA and SEP-Pak® method are significantly different (p = 0.026). The RCP obtained by TLC SA and W 1 and 3 MM methods are also significantly different (p w1 = 0.041, p w3 &amp;lt; 0.0001). The RCP obtained by either TLC SA or HPLC method are not significantly different (p = 0.497) Conclusions : A new HPLC method was developed for the control of the RCP 99mTc-tetrofosmin. The other methods differ from RCP (reference method). Whatman methods overestimate RCP values versus TLC SA or HPLC method. This study allows us to improve the detection of the cardiotoxic side effects due to chemotherapy more quickly than TLC SA method and permits early prevention of toxicity by dose adjustment of anticancer drugs. Citation Format: Olivier Madar, Keyvan Rezaï, Emmanuelle Ledauphin, Eve Camps, Catherine Tainturier, Francois Lokiec. Comparison of different methods for radiochemical purity (RCP) control of 99mTc-tetrofosminin oncology. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2677. doi:10.1158/1538-7445.AM2013-2677

The Presence of Sodium Nitrate in Generator Eluate Decreases the Radiochemical Purity of 99mTc-Sestamibi

A high radiochemical purity (RCP) is recommended for radiopharmaceutical compounds used in the clinical practice of nuclear medicine. However, some preparations of (99m)Tc-sestamibi contain excess impurities (>6%). To understand the origin of these impurities, we investigated the effect of sodium nitrate on the RCP of sestamibi preparations by testing eluates from 3 commercially available (99m)Tc generators. The sestamibi kits (Stamicis) were reconstituted with (99m)Tc eluate from nitrate-containing wet-column (NCWC), nitrate-free wet-column (NFWC), and nitrate-free dry-column (NFDC) generators. Sodium nitrate was 0.05 mg/mL in eluates from the NCWC generators. The RCP was determined using aluminum oxide sheets as the stationary phase and absolute ethanol as the mobile phase. Succimer, tetrofosmin, oxidronate, exametazine, albumin nanocolloid, and soluble albumin were also tested for their RCP values with eluates from the 3 different (99m)Tc generators. The RCP assessment of (99m)Tc-sestamibi was performed on 127 Stamicis preparations. Significantly lower RCP values were found for Stamicis kits prepared with the NCWC generator than for Stamicis prepared with the NFWC (P < 0.0001) and NFDC (P < 0.0001) generators. The number of Stamicis preparations with an RCP under 94% was greater with the NCWC generator (32 of 53 kits) than with the NFDC (2 of 51 kits) or NFWC (0 of 23 kits) generator. Furthermore, the addition of a 0.05 mg/mL concentration of nitrate in NFWC generator eluates significantly decreased the RCP of the Stamicis preparation. In the absence of nitrate in (99m)Tc eluate, no difference was observed between the RCP values of Stamicis kits prepared with the NFWC and NFDC generators. The (99m)Tc impurities generated by nitrates did not modify the quality of myocardial imaging (normal heart-to-lung ratio, 2.2), probably because these impurities are not in the heart field of view. No other tested (99m)Tc-radiopharmaceutical interfered with nitrates. We recommend using nitrate-free generator eluates in (99m)Tc-sestamibi preparations to improve the product quality and prevent unnecessary exposure of the patient to radiation.

Synthesis of 11C-labeled Kendine 91, a histone deacetylase inhibitor

In the present paper, the synthesis of 11C-labeled Kendine 91 (a HDAC inhibitor which has shown in vitro and in vivo activity in HCT 116 and MOLT 4 human cancer cell lines) is described for the first time. The radiosynthesis has been approached by reaction of the non-radioactive precursor 6-((3-(4-hydroxyphenyl)-5-phenyl-1H-pyrrole-2-carboxamide))hexanehydroxamic acid with [11C]CH3I in basic media. Despite the presence of more than one reactive site in the chemical structure of the precursor, acceptable radiochemical yield (8.2±2.1%, decay corrected to the end of bombardment), specific activity (28.2±9.4GBq/μmol) and radiochemical purity values (>95%) were obtained in reasonably short preparation times (∼40min). Despite the moderate radiochemical yield, final radioactivity and radioactivity concentration values (1.8±0.3GBq and 180MBq/ml, respectively) should be sufficient for putative in vivo studies in animals.

A new method for the radiochemical purity measurement of 111In-pentetreotide

The recommended method for the measurement of radiochemical purity (RCP) of ¹¹¹In-labelled pentetreotide is thin-layer chromatography with a silica gel as the stationary phase and a 0.1 N sodium citrate solution (pH 5) as the mobile phase. According to the supplier's instructions, the mobile phase must be prepared before the test is carried out, and the recommended stationary phase is off-market. We propose a new method for RCP measurement in which the mobile phase is acid citrate dextrose, solution A, which does not need to be prepared beforehand, and thin-layer chromatography is performed with a silica gel-impregnated glass fibre sheet as the stationary phase. We used both methods to measure the percentages of radiopharmaceutical and impurities. The range of RCP values obtained was 98.0-99.9% (mean=99.3%) by the standard method and 98.1-99.9% (mean=99.2%) by the new method. We observed no differences between the RCP values of both methods (P=0.070). The proposed method is suitable for RCP testing because it yields results that are in good agreement with those of the standard method and because it is easier to perform as the mobile-phase solution need not be prepared in advance.

Evaluation of alternative methods for radiochemical purity testing of indium-111 capromab pendetide

ObjectiveTo evaluate alternative methods for radiochemical purity testing of indium (In)-111 capromab pendetide after the discontinuation of instant thin-layer chromatography silica gel (ITLC-SG) strips. DesignDescriptive experimental study. SettingUnited States in 2009. ParticipantsNot applicable. InterventionPaper chromatography using Whatman 3MM strips, paper chromatography using Whatman 31ET strips, and mini-column chromatography using silica Sep-Pak cartridges were evaluated in the radiochemical purity testing of 13 consecutive vials of In-111 capromab pendetide prepared for clinical patient imaging procedures. These methods also were evaluated by testing seven aliquots of In-111 capromab pendetide that had been spiked with 5% to 15% In-111 pentetate (diethylene triamine pentaacetic acid). Main outcome measuresCorrelation coefficients, radiochemical purity values for each method compared with ITLC-SG, and procedure times. ResultsCorrelation coefficients of 0.988, 0.996, and 0.979 were found for ITLC-SG compared with Whatman 3MM, Whatman 31ET, and silica Sep-Pak, respectively. Compared with ITLC-SG, mean (±SD) radiochemical purity values differed by −0.8± (range −2.5 to 0.4) for Whatman 3MM, −0.8± (–2.3 to 0) for Whatman 31ET, and −0.5± (–3.6 to 0.7) for silica Sep-Pak. The approximate time required to develop the chromatography strip or elute the mini-column was 3, 14, 5, and 6 minutes for ITLC-SG, Whatman 3MM, Whatman 31ET, and silica Sep-Pak, respectively. ConclusionAll three methods evaluated were acceptable alternatives to ITLC-SG for radiochemical purity testing of In-111 capromab pendetide. Based on its slightly higher correlation to ITLC-SG, slightly tighter SD and range, and slightly shorter development time, Whatman 31ET is preferred in our facility.

An Optimised Radiolabel Procedure to Prepare 99mTc-Colloidal Rhenium Sulphide to Improve Radiochemical Purity

More than 25% of 99mTc colloidal rhenium sulphide preparations have been reported to have a radiochemical purity of <95% in 11 radiopharmacies. To identify the key parameters involved in radiochemical purity, different preparation procedures were analysed to develop an optimised preparation method. In the first part of this study, various data such as the Nanocis kit batch number, the eluate volume, the time between the two final elutions, the temperature and duration of heating were collected and analysed to determine the critical parameters that significantly decrease radiochemical purity. In the second part, a new procedure was applied and then the same parameters and radiochemical purity values were collected and compared with the results before the new procedure. Among 184 preparations, 137 (75%) had a radiochemical purity exceeding 95%, 25 (13.6%) were between 90 and 95% pure and 22 (12%) were below 90%. Significantly higher radiochemical purity was observed after the implementation of the new preparation procedure (89.5% of 374 preparations had radiochemical purities of > 95%). This new procedure consists in lowering the 99mTc eluate volume and time of heating. The implementation of a new method for the preparation of (99m)Tc colloidal rhenium sulphide based on a comparison of practices in various radiopharmacies resulted in: i) a determination of the critical points of this preparation, ii) an optimised labelling technique to harmonise different practices, and iii) a significant improvement in the preparations radiochemical purity and the quality of the lymphoscintigraphy in the location of sentinel node.

Radiosynthesis and biodistribution of the 99mTc-trovafloxacin complex as a potential methicillin resistant Staphylococcus aureus infection radiotracer

In the current investigation radiosynthesis of the 99mTc-trovafloxacin (99mTc-TVN) complex and its biodistribution in male Wistar rats (MWR) artificially infected with live and heat killed methicillin resistant Staphylococcus aureus (MRSA) was studied. Further the complex was evaluated in terms of the radiochemical stability in normal saline, in vitro stability in serum and in vitro binding with MRSA. The complex showed radiochemical purity (RCP) in normal saline with a maximum value of 97.30 ± 0.52% at 30 min after its reconstitution. The RCP value went down to 90.45 ± 0.48% within 4 h. In serum at 37 °C, the complex showed permanence up to 4 h but within 16 h of incubation the production of undesirable side product of 17.25% (free and radio-colloid) was observed. In buffer the labeled TVN showed saturated in vitro binding with live MRSA. The uptake of the complex in the thigh of the MWR infected with live MRSA was almost five fold than those infected with heat killed MRSA. The high RCP values, in vitro stability in serum, saturated in vitro binding with MRSA and promising biodistribution with six fold higher accumulation in the infected organ of the MWR infected with live MRSA established the usefulness of the 99mTc-TVN as a promising MRSA infection radiotracer.

Radiosynthesis and biodistribution of 99mTc-tricarbonyl complex of temafloxacin dithiocarbamate: a potential Streptococci pneumoniae infection radiotracer

In the current investigation the complexation of derivatized temafloxacin with 99mTc using [99mTc(CO)3(H2O)3]+ precursor was assessed. The tricarbonyl complex of the temafloxacin dithiocarbamate (99mTc(CO)3-TAND) was characterized in terms of radiochemical purity (RCP) yield in saline, in vitro radiochemical stability in serum, in vitro binding with Streptococci pneumoniae and biodistribution in male Wister rats (MWR) artificially infected with living and heat killed Streptococci pneumoniae. The 99mTc(CO)3-TAND complex showed 98.10 ± 15% RCP value at 30 min of the reconstitution and remained more than 90% stable up to 120 min in normal saline at room temperature. In serum a stable behavior with the appearance of 15.30% unwanted side product up to 16 h of incubation was observed. A saturated in vitro binding with Streptococci pneumoniae was observed. The complex showed almost six times higher uptake in the infected muscle as compared to the inflamed and normal muscles of the MWR infected with living Streptococci pneumoniae. Insignificant difference in the uptake of the tracer in the infected, inflamed and normal muscles of the MWR infected with heat killed Streptococci pneumoniae was noted. Based on the elevated RCP in saline, in vitro stability in serum at 37 °C, saturated in vitro binding with pathogens and better biodistribution behavior with higher accumulation of the tracer in target organs confirmed the suitability of the 99mTc(CO)3-TAND complex as promising infection radiotracer.

Synthesis of 99mTcV ≡ N-Pazufloxacin dithiocarbamate complex and biological evaluation in Wister rats artificially infected with Escherichia coli

99mTc ≡ N-Pazufloxacin dithiocarbamate (99mTc ≡ N-PZN) complex was synthesized through the [99mTc ≡ N]2+ core and its aptness was radiochemically and biologically evaluated in terms of radiochemical purity (RCP) in saline, in vitro stability in serum, in vitro bacterial uptake and percent in vivo uptake in male Wister rats (MWR) artificially infected with alive and heat killed Escherichia coli (E. coli). The 99mTc ≡ N-PZN complex showed more than 90% RCP up to 4 h after reconstitution in normal saline at room temperature with a maximum RCP value of 98.40 ± 0.28% (at 30 min). At 37 °C in serum the complex showed stable behaviour up to 4 h with the appearance of 15.95% undesirable by products within 16 h of the incubation. The complex showed saturated in vitro binding with E. coli with a maximum uptake of 74.25 ± 0.50% (at 90 min). Normal biodistribution behaviour was noted with a sixfold higher accumulation in the muscle of the MWR, artificially infected with live E. coli as compared to the MWR infected with heat killed E. coli, inflamed and normal muscle. The high RCP in saline, elevated in vitro stability in serum, saturated in vitro binding with E. coli and the sixfold higher accumulation in the infected (live) muscle of the MWR as compared to the inflamed and normal muscle, recognized the aptness of the 99mTc ≡ N-PZND complex as a prospective E. coli in vivo infection radiotracer.