Routine Production Research Articles

Crystal Defect Investigation in PVT-Grown ZnSe Under Different Seeding Conditions and Growth Configurations Using Synchrotron X-Ray Topography

Zinc selenide (ZnSe) is a widely utilized II-VI semiconducting material for fabricating high-performance optoelectronics devices owing to its unique electrical and optical properties. As those properties highly depend on the native point defects and impurity distribution, achieving routine production of high-quality ZnSe crystal is essential. This study conducted synchrotron white beam X-ray topography (SWBXT), optical microscopy and high-resolution triple X-ray diffraction (HRTXD) characterization on five as-grown ZnSe boules grown in physical vapor transport (PVT) method with different seeding conditions and growth configurations. Study indicated that nucleation of multiple grains is induced during seeded growth, while self-seeded boules tend to obtain single crystals. ZnSe boules grown in vertical configuration are found to have relatively poor crystalline quality comparing to horizontally grown boules that are characterized by low energy facets. The twinning mechanism is also discussed. This study successfully investigated factors that induce crystal quality variation during the growth process.

Study of the automated synthesis of the radiopharmaceutical fluoroestradiol-18F

Approximately 75% of breast cancer cells express estrogen receptor positive, being the second leading cause of cancer death among women worldwide with an incidence of 25% per year. 16α-[18F]-fluoro-17β-estradiol, FES-18F, is a radiopharmaceutical that binds to estrogen receptors enabling the acquisition of molecular images for non-invasive diagnosis of primary and metastatic breast cancer using PET-CT. The objective of this work was to study the synthesis of FES-18F in the GE TRACERlab® MXFDG module, using the chemical kit and the ABX® disposable cassette, and to determine the process yield and the analytical parameters to be used in the routine production of this radiopharmaceutical. Automated synthesis occurs in 75 minutes and includes percolation of [18F-] fluoride into an anion exchange cartridge, cartridge elution, 3-step azeotropic drying, labeling using precursor 3-methoxymethyl-16β,17β-epiestriol-O-cyclic sulfone (MMSE) and a hydrolysis step. Product purification is done in the module using solid phase extraction (SPE) cartridges. The radiochemical yield was reproductive, regardless of fluor-18 activity at entry into the module, and the results of quality control tests suggest that the radiopharmaceutical meets the criteria established for other fluor-18-labelled radiopharmaceuticals that have monographs in official compendiums. In vivo biodistribution studies in healthy animals and with a tumor model developed with MCF-7 cells, demonstrated radiopharmaceutical uptake in excretory organs and specificity for breast tumor cells.

Development of a global annual land surface phenology dataset for 1982–2018 from the AVHRR data by implementing multiple phenology retrieving methods

The land surface phenology (LSP) associated with vegetation dynamics plays an important role in influencing the land surface processes and land–atmosphere interactions. Satellite observations have been widely used in studies for the monitoring of LSP across large areas based on different phenology retrieval algorithms and the routine production of LSP from remote sensing data has yet come to fruition. Here we used six phenology retrieval methods, including the amplitude threshold (AT), first-order derivative (FOD), second-order derivative (SOD), relative changing rate (RCR), third-order derivative (TOD), and curvature change rate (CCR), to retrieve the start of the growing season (SOS) and the end of the growing season (EOS) from the Advanced Very High Resolution Radiometer (AVHRR) data. We improved the curve fitting method to reduce uncertainties owing to data preprocessing. The results indicated that both SOS and EOS retrieved by six different methods had similar spatial distribution and the retrieved dates could vary largely at the pixel level. In the Northern Hemisphere, from 1982 to 2018, the trends of SOS retrieved vary across methods and only the EOS extracted by the relative change curvature method had a significant advanced trend. In the Southern Hemisphere, from 1982 to 2018, SOS results derived from four methods (i.e., AT, SOD, TOD, and CCR) showed significantly delayed trends, EOS results extracted by all the methods demonstrated insignificant trends. The phenology retrieval methods were assessed using the field observation data from the Pan European Phenology Project (PEP725) and from time series of leaf area index (LAI) measured at flux towers. The satellite-retrieved dates of both SOS and EOS were positively correlated with field observation and the relationships are largely dependent on how field phenology metrics are defined. We presented longer time series (1982–2018) data of phenology metrics with fewer gaps and multiple phenology retrieving methods as compared to the MODIS land cover dynamics product. Based on our assessments, one might use the SOS generated by FOD and the EOS generated by RCR as they provide results the most consistent with field data among all the tested methods. If studies aim to use the earliest SOS (or latest EOS) in a year, one might use the data retrieved based on TOD or CCR. The global dataset is delivered for uses in studies and applications associated with LSP.

CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research

The malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialised cells. Here, we engineer P. falciparum NF54 inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes via conditional overexpression of the sexual commitment factor GDV1. NF54/iGP lines consistently achieve sexual commitment rates of 75% and produce viable gametocytes that are transmissible by mosquitoes. We also demonstrate that further genetic engineering of NF54/iGP parasites is a valuable tool for the targeted exploration of gametocyte biology. In summary, we believe the iGP approach developed here will greatly expedite basic and applied malaria transmission stage research.

Heavy-ion production of 77Br and 76Br

Many radioisotopes with potential medical applications are difficult to produce routinely, especially those on the proton-rich side of the valley of stability. Current production methods typically use light-ion (protons or deuteron) reactions on materials of similar mass to the target radioisotope, which limits the elemental target material available and may require the use of targets with poor thermal properties (as is the case for the production of radiobromine). These reactions may also create significant amounts of proton-rich decay products which require chemical separation from the desired product in a highly radioactive environment. A promising alternative method using heavy-ion fusion-evaporation reactions for the production of the medically relevant bromine radioisotopes 76Br (t1/2 = 16.2 h) and 77Br (t1/2 = 57.0 h) is presented. Heavy-ion beams of 28Si and 16O were used to bombard natural chromium and copper targets just above the Coulomb barrier at the University of Notre Dame's Nuclear Science Laboratory to produce these bromine and precursor radioisotopes by fusion-evaporation reactions. Production yields for these reactions were measured and compared to PACE4 calculations. In addition to using more robust targets for irradiation, a simple physical–chemical separation method is proposed that will lead to very high radiopurity yields. A summary of accelerator facility requirements needed for routine production of these radioisotopes is also presented.

Serum index rules prevent risk of analysing uncentrifuged tubes on automated biochemistry analysers

Around 1.5% of the total clinical biochemistry tests performed in laboratories are affected by preanalytical errors. Large, automated chemistry analysers prevent errors and interference by using control systems such as spectrophotometric measurements to evaluate serum indices, i.e. haemolysis (H), icterus (I), and lipemia/turbidity (L). However, still preanalytical errors can remain undetected. Our laboratory experienced an incident caused by laboratory-induced preanalytical errors, where approximately 100 sedimented lithium heparin samples bypassed centrifugation and entered our automated analyser. Based on index results, we investigated the possibility of using turbidimetry measurement, as a mean to prevent analysis on uncentrifuged sedimented whole blood. 14078 L-indices from 8 days in August 2019 were extracted from the middleware and used to develop and evaluate stop rules. Similarly, a one-day validation dataset was identified in December 2020 and used for an independent validation. Three different types of stop rules were evaluated: (1) A single L-index result above a cut-off; (2) A sequence of an L-index results above a cut-off; (3) A simple moving average of n results above a cut-off. A stop rule using 3 consecutive L-indices of 40–60 was found to be superior. However, practical implementation in the instrument middleware on a Roche Cobas 8000 only allowed a simple moving average of 110 (n = 5). This rule was found to be able to identify and stop sedimented whole blood analysis. Additionally, the rule has minimal impact on daily routine production in the laboratory.

Consumer awareness on pre-packaged food labelling information towards the purchase of the pre-packaged food products

This study determined the level of awareness on pre-packaged food labelling information among consumers. A cross-sectional survey design was used to gather information from respondents. Purposively sampling method was used to select the TFDA registered supermarkets, provision shops and other pre-packaged food corner outlets. A systematic randomly sampling was used to interview respondents from the main outlets of the shops. A questionnaire with both close and open ended questions was used to collect information from 150 consumers who were found in the supermarket, provision shops and other pre-packaged food outlets purchasing pre-packaged food products. Descriptive statistics and the chi-square tests of significance were employed to determine the association between variables. The findings revealed that consumers were moderately aware on the use of pre-packaged food labelling information. The findings further revealed some difficulties encountered by consumers while reading food labels include technical language used, small font size when reading food label, unfamiliar language as well as incomplete labelling information. Circumstances in which consumers purchase pre-packaged food without consulting the respective labels include time constraint and purchase of routine food products. The findings revealed that respondents level of education was significantly associated with respondents awareness on the use of pre-packaged food labelling information. The findings further revealed that respondent level of education and their occupation were significantly associated with the importance of using pre-packaged food labelling information. Due to public health concern on human being, it is therefore recommended that deliberate efforts should be taken to use educational activities in order to raise consumer awareness on reading and using of pre-packaged food labelling information prior to purchase.

GMP-compliant production of [68Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor

Background[68Ga]Ga-NeoB is a novel DOTA-coupled Gastrin Releasing Peptide Receptor (GRPR) antagonist with high affinity for GRPR and good in vivo stability. This study aimed at (1) the translation of preclinical results to the clinics and establish the preparation of [68Ga]Ga-NeoB using a GMP conform kit approach and a licensed 68Ge/68Ga generator and (2) to explore the application of [68Ga]Ga-NeoB in patients with gastrointestinal stromal tumors (GIST) before and/or after interventional treatment (selective internal radiotherapy, irreversible electroporation, microwave ablation).ResultsValidation of the production and quality control of [68Ga]Ga-NeoB for patient use had to be performed before starting the GMP production. Six independent batches of [68Ga]Ga-NeoB were produced, all met the quality and sterility criteria and yielded 712 ± 73 MBq of the radiotracer in a radiochemical purity of > 95% and a molar activity of 14.2 ± 1.5 GBq/μmol within 20 min synthesis time and additional 20 min quality control. Three patients (2 females, 1 male, 51–77 yrs. of age) with progressive gastrointestinal stromal tumor metastases in the liver or peritoneum not responsive to standard tyrosine kinase inhibitor therapy underwent both [68Ga]Ga-NeoB scans prior and after interventional therapy. Radiosynthesis of 68Ga-NeoB was performed using a kit approach under GMP conditions. No specific patient preparation such as fasting or hydration was required for [68Ga]Ga-NeoB PET/CT imaging. Contrast-enhanced PET/CT studies were performed. A delayed, second abdominal image after the administration of the of [68Ga]Ga-NeoB was acquired at 120 min post injection.ConclusionsA fully GMP compliant kit preparation of [68Ga]Ga-NeoB enabling the routine production of the tracer under GMP conditions was established for clinical routine PET/CT imaging of patients with metastatic GIST and proved to adequately visualize tumor deposits in the abdomen expressing GRPR. Patients could benefit from additional information derived from [68Ga]Ga-NeoB diagnosis to assess the presence of GRPR in the tumor tissue and monitor antitumor treatment.

Fracture Propagation and Hydraulic Properties of a Coal Floor Subjected to Thick-Seam Longwalling above a Highly Confined Aquifer

The high-pressure and water-rich confined aquifer occurring in the Ordovician limestone sequence poses great threats to the routine production of underground longwall mining. Considering the intense cooperation of mining disturbance and water pressure, water-conducting fractures within a coal seam floor can connect the lower aquifer and upper goaf, and this hydraulic behavior is considered the root of water inrush hazard and water loss or contamination. In this paper, the panel 4301 of the Longquan coal mine serves as the case where the panel works closely above the floor with high water pressure. By the combination of physical and numerical modelling approaches, the variation characteristics of fracture development and volumetric strain of floor rocks subjected to mining disturbance are analyzed. A numerical computation model is constructed based on the volumetric strain-permeability equation obtained by curve fitting, and on such basis, the impacts of different mining parameters on floor rock permeability are studied. The results show that the floor rocks experience fracture generation, extension, and convergence procedures as the workface advances along the longitudinal direction, and fractures appearing in front of the workface are more developed. In the whole process of coal seam extraction, the volumetric strain profile exhibits “Λ” shape and an inverted saddle shape before and after overburden strata collapse. By controlling a single variable, the paper reveals that panel height is of greater impact on floor permeability changes than panel length and panel width.

Geniac: Automatic Configuration GENerator and Installer for nextflow pipelines

With the advent of high-throughput biotechnological platforms and their ever-growing capacity, life science has turned into a digitized, computational and data-intensive discipline. As a consequence, standard analysis with a bioinformatics pipeline in the context of routine production has become a challenge such that the data can be processed in real-time and delivered to the end-users as fast as possible. The usage of workflow management systems along with packaging systems and containerization technologies offer an opportunity to tackle this challenge. While very powerful, they can be used and combined in multiple ways thus increasing their usage complexity. Therefore, guidelines and protocols are required in order to detail how the source code of the bioinformatics pipeline should be written and organized to ensure its usability, maintainability, interoperability, sustainability, portability, reproducibility, scalability and efficiency. Capitalizing on Nextflow, Conda, Docker, Singularity and the nf-core initiative, we propose a set of best practices along the development life cycle of the bioinformatics pipeline and deployment for production operations which address different expert communities including i) the bioinformaticians and statisticians ii) the software engineers and iii) the data managers and core facility engineers. We implemented Geniac (Automatic Configuration GENerator and Installer for nextflow pipelines) which consists of a toolbox with three components: i) a technical documentation available at https://geniac.readthedocs.io to detail coding guidelines for the bioinformatics pipeline with Nextflow, ii) a linter to check that the code respects the guidelines, and iii) an add-on to generate configuration files, build the containers and deploy the pipeline. The Geniac toolbox aims at the harmonization of development practices across developers and automation of the generation of configuration files and containers by parsing the source code of the Nextflow pipeline. The Geniac toolbox and two demo pipelines are available on GitHub. This article presents the main functionalities of Geniac.

Integration of food waste composting and vegetable gardens in a university campus

Local composting (household, community and small scale applications) is considered a sustainable option for bio-waste recovery and is receiving increasing demand from society. Higher education institutions are no exception, but detailed and comprehensive long-term studies on composting programs on university campuses are lacking. The local composting program of the University of A Coruña (UDC) offers a decentralized service for the treatment of food waste from 11 university canteens using static and dynamic composters located in 9 different composting areas. Considering the three pillars of sustainability, this work describes the characteristics of the different composting technologies used and their investment and operational costs, the routine monitoring process and product quality, the integration of the composting systems as living labs for biotechnology and environmental engineering courses, and the use of compost in the university vegetable gardens. The agents involved in the project are the canteen staff, the university gardening company, external composting operators, university researchers and teachers, sustainability scholarship students and volunteer people. Organic waste is usually delivered directly by canteen staff to composters. The gardening service provides green waste from UDC campus (crushed pruning) that is used as bulking material. The monitoring and maintenance of the composting areas is currently in charge of external staff provided by a local NGO dedicated to cooperation and job reintegration of the unemployed. The service also allows the incorporation of volunteers and scholarship students as operators and process monitoring supervisors. The main result of this project was the prevention of a large amount of waste that did not require collection and transportation, or disposal or incineration. This is being done in an economically sustainable way, as decentralized composting costs have been lower than the average costs of municipal solid waste treatment in the region. The lower investment costs of static composters largely offset the higher labour costs and result in lower overall costs than those of the dynamic composter. The dissemination of composting practice to society was another important outcome of the project.

Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine

A novel, genetically-stabilized type 2 oral polio vaccine (nOPV2), developed to assist in the global polio eradication program, was recently the first-ever vaccine granted Emergency Use Listing by the WHO. Lot release tests for this vaccine included—for the first time to our knowledge—the assessment of genetic heterogeneity using next-generation sequencing (NGS). NGS ensures that the genetically-modified regions of the vaccine virus genome remain as designed and that levels of polymorphisms which may impact safety or efficacy are controlled during routine production. The variants present in nOPV2 lots were first assessed for temperature sensitivity and neurovirulence using molecular clones to inform which polymorphisms warranted formal evaluation during lot release. The novel use of NGS as a lot release test required formal validation of the method. Analysis of an nOPV2 lot spiked with the parental Sabin-2 strain enabled performance characteristics of the method to be assessed simultaneously at over 40 positions in the genome. These characteristics included repeatability and intermediate precision of polymorphism measurement, linearity of both spike-induced and nOPV2 lot-specific polymorphisms, and the limit-of-detection of spike-induced polymorphisms. The performance characteristics of the method met pre-defined criteria for 34 spike-induced polymorphic sites and 8 polymorphisms associated with the nOPV2 preparation; these sites collectively spanned most of the viral genome. Finally, the co-location of variants of interest on genomes was evaluated, with implications for the interpretation of NGS discussed.

An Autoinducible Plasmid Equipped with a Stationary Phase Promoter for Recombinant Protein Production

The expression of recombinant proteins in E. coli includes various factors each of which plays a critical role sometimes. The typical procedure to produce heterologous proteins consists of the following steps: (1) construction of an overexpression plasmid by insertion of the target gene into a suitable vector, (2) transformation of a proper strain for protein production with the constructed plasmid, (3) growth of the host in a proper medium and the induction of the protein production at a proper timing, and (4) further growth to get the highest possible yield. We constructed an expression plasmid with an autoinducible promoter working in a general host that was not designed for protein production, and in a TB medium which is much easier to prepare compared to the sofisticated defined medium. This plasmid also contains a color indicator which turns red as the protein is produced. Since the plasmid works with general hosts, one can directly go to the production stage right after selecting the colony with the correctly constructed plasmid. With some experience, one can decide when to harvest the culture. We hope that this plasmid will help researchers to save their time and effort in a routine protein production procedure.

A methodology to enhance thermal neutron flux in Tehran Research Reactor core for domestic fuel test purposes

Performance of newly fabricated nuclear fuels must be tested under desired neutronic and thermal-hydraulic operating conditions prior to utilization in the reactor core. Tehran research reactor (TRR) as an MTR-type reactor is the only operating research reactor in the country that can potentially be used for irradiation tests on domestic fuels. In this study, compacting TRR core configuration, as a method to increase thermal neutron flux in the central in-core irradiation position to provide desired neutronic environment for fuel irradiation tests, is of concern. Several design criteria and limitations, including preservation of enough and suitable irradiation positions in the core for routine radioisotopes production activities of the reactor, have been considered to develop a new compact core configuration for TRR in which, desired linear heat generation rate is achieved in the test fuels and all the neutronic and thermal-hydraulic safety parameters of the proposed configuration are in accordance with the acceptance criteria stated in the reactor FSAR.

Establishing the [18F]-FDG Production via Two Different Automated Synthesizers for Routine Clinical Studies: Our Institutional Experiences of 4 years.

Introduction:[18F]-Fluorodeoxyglucose ([18F]-FDG) is the most widely used positron-emission tomography tracer used for imaging in clinical studies such as early detection of cancer or its malignancies, quantifications, staging, and restaging of several malignancies. For clinical application, routine production of this tracer is mandatory in compliance to regulatory guidelines. Several dedicated commercial synthesizers are currently used for producing[18F]-FDG for clinical usage. Being at hospital radiopharmacy, it is our responsibility and duty to support the clinical service with uninterrupted production and supply of [18F]-FDG. This document describes the production of [18F]-FDG using two different automated synthesizers in terms of its production yield, time of synthesis, and analyze the quality control (QC) of the produced [18F]-FDG.Materials and Methods:The precursor, mannose triflate ultra-pure, authentic nonradioactive standard FDG and [18O]-water were obtained from ABX, Germany. Solvents and reagents were purchased from Sigma Aldrich India Ltd. and Fisher Scientific India Ltd., (Mumbai, Maharashtra, India).Results:The protocol developed for the synthesis with MPS-100 synthesizer yield of [18F]-FDG is approximate about 45% End of Bombardment (EOB) with synthesis time of around 35 min, whereas with F300E synthesizer it is around 60% with synthesis time of 25 min. The quality of the tracer produced by both synthesizers is at par with the QC parameter for clinical applications.Conclusions:Finally, we have developed the production using two automated synthesis modules which have the capability to produce [18F]-FDG, to do the patient studies in good yield and purity. Our protocol is simple, reproducible, and robust.

“The Good, the Bad and the Ugly” in the First Year of COVID-19 Pandemic

During the first year of COVID-19 pandemic, while there have been rapid developments in diagnosis and treatment of the disease;drug interactions and side effects have created a problem especially in high risk patients with chronic diseases and multiple drug use. In contrast to the routine vaccine production process, SARS-CoV-2 vaccines have been developed in a short period of time by many pharmaceutical companies, and community vaccination has started in many countries. However, this process is restricted by mutation and problems in production and distribution. The fact that the pathophysiology of the disease has not been fully elucidated has brought the prolonged COVID-19 syndrome definition to our clinical practice. Positive improvements and negative aspects that we have encountered so far in the first year of this new pandemic reminded us the great film by Sergio Leone: “The Good, The Bad and The Ugly”. So, we decided to cover these aspects under the same headings. Gaining an overview of the many developments, problems and solution ideas we encountered and witnessed during the pandemic year will make the management of the process easier.

Media Fill Test for Validation of Non-Radioactive Kit for Radiopharmaceutical Preparations

The administration of improperly prepared intravenous fluids might determine healthcare-associated infections. Quality and sterility assurance in radiopharmaceutical manufacturing products must be evaluated by media fill tests that simulate the performance of the aseptic manufacturing procedure. The aim of this study is to show a methodological modification of a specific step of media fill tests, giving an overview of economic and organizational advantages that it might bring. Media fill tests were conducted to ensure that they reproduce as strictly as possible the routine aseptic production process with all the critical steps described in the internal Standard Operating Procedures. We introduced an innovative modification in step 1: instead of using a completely decayed 99Mo/99mTc generator, we used a99Mo/99mTc generator just before its disposal, eluting it with saline solution aspirated in an empty vacuum vial. A total of 47 production runs were performed, and a total of 799 vials were tested for sterility. Thirteen nuclear medicine technicians were assessed. We found contamination in 1% of the total number of vials analyzed. The modification proposed shows several advantages: reduction of the costs of the media fill tests, the possibility to manage these without referring to external services, and decreased injuries for technicians who perform the tests.

Humanoid robot adoption and labour productivity: a perspective on ambidextrous product innovation routines

The increasing presence of humanoid robot adoption has generated a change in explorative and exploitative routines. If the explorative routines provoke creativity and critical thinking which are delivered by humans, exploitative routines induce repetitive actions and mimic activities which are executed by humanoids. This has raised the need for a better balance between both routines involving an ambidextrous dynamic process. Here, product innovations play a relevant role in enhancing such balance and labour productivity. If, from the conceptual standpoint, this phenomenon has already been explored, there is still the need to empirically analyse it. We thus offer a meso-analysis of twenty-four countries located in Europe through the lens of the Service Robot Deployment (SRD) Model and the conceptual lens of organizational ambidexterity. By a regression methodology, the results show that humanoid robot adoption is still not affecting labour productivity which, by contrast, is positively and significantly connected with both radically new and marginally modified/unchanged production of innovative routines. Our original contribution, which falls in the field of Human Resources Management and Artificial Intelligence, is that humanoids are not directly impacting labour productivity but indirectly through the generation of both new and marginally modified (or unchanged) routines. This situation persuades senior leaders to achieve a balance between exploitative and explorative product innovation routines. Supplemental data for this article is available online at https://doi.org/10.1080/09585192.2021.1897643 .

Automated synthesis of [18F]Ga-rhPSMA-7/ -7.3: results, quality control and experience from more than 200 routine productions

IntroductionThe radiohybrid (rh) prostate-specific membrane antigen (PSMA)-targeted ligand [18F]Ga-rhPSMA-7 has previously been clinically assessed and demonstrated promising results for PET-imaging of prostate cancer. The ligand is present as a mixture of four stereoisomers ([18F]Ga-rhPSMA-7.1, − 7.2, − 7.3 and − 7.4) and after a preclinical isomer selection process, [18F]Ga-rhPSMA-7.3 has entered formal clinical trials. Here we report on the establishment of a fully automated production process for large-scale production of [18F]Ga-rhPSMA-7/ -7.3 under GMP conditions (EudraLex).Methods[18F]Fluoride in highly enriched [18O]H2O was retained on a strong anion exchange cartridge, rinsed with anhydrous acetonitrile and subsequently eluted with a solution of [K+ ⊂ 2.2.2]OH− in anhydrous acetonitrile into a reactor containing Ga-rhPSMA ligand and oxalic acid in DMSO. 18F-for-19F isotopic exchange at the Silicon-Fluoride Acceptor (SiFA) was performed at room temperature, followed by dilution with buffer and cartridge-based purification. Optimum process parameters were determined on the laboratory scale and thereafter implemented into an automated synthesis. Data for radiochemical yield (RCY), purity and quality control were analyzed for 243 clinical productions (160 for [18F]Ga-rhPSMA-7; 83 for [18F]Ga-rhPSMA-7.3).ResultsThe automated production of [18F]Ga-rhPSMA-7 and the single isomer [18F]Ga-rhPSMA-7.3 is completed in approx. 16 min with an average RCY of 49.2 ± 8.6% and an excellent reliability of 98.8%. Based on the different starting activities (range: 31–130 GBq, 89 ± 14 GBq) an average molar activity of 291 ± 62 GBq/μmol (range: 50–450 GBq/μmol) was reached for labeling of 150 nmol (231 μg) precursor. Radiochemical purity, as measured by radio-high performance liquid chromatography and radio-thin layer chromatography, was 99.9 ± 0.2% and 97.8 ± 1.0%, respectively.ConclusionThis investigation demonstrates that 18F-for-19F isotopic exchange is well suited for the fast, efficient and reliable automated routine production of 18F-labeled PSMA-targeted ligands. Due to its simplicity, speed and robustness the development of further SiFA-based radiopharmaceuticals is highly promising and can be of far-reaching importance for future theranostic concepts.

Analysis of α-Tocopherol Stereoisomers in Fortified Infant Formula by Chiral Chromatography.

Direct measurement of the bioavailable α-tocopherol content presents a significant analytical challenge and requires chiral separation of the α-tocopherol stereoisomers. The objective of the study was to validate an analytical method for the analysis of α-tocopherol stereoisomers in infant formulas and dairy products. Samples were saponified at elevated temperature and lipophilic components were extracted into an organic solvent, with subsequent chromatographic separation of the α-tocopherol stereoisomers achieved by HPLC with a chiral column and fluorescence detection. The method was shown to be accurate, with spike recoveries of 91.9-108.8% for RRR-α-tocopherol and 90.1-104.7% for α-tocopherol, with no statistical bias against NIST 1849a certified reference material (P-value = 0.54) and an HPLC-UV analytical method (P-value = 0.48). Acceptable precision was confirmed, with repeatabilities estimated at 3.5% RSDr (HorRat = 0.6) for RRR-α-tocopherol and 4.6% RSDr (HorRat = 0.4) for α-tocopherol. A straightforward chiral chromatographic method for the analysis of stereoisomeric forms of α-tocopherol is described. In a single analytical run, the method can quantify: (i) the total α-tocopherol content; (ii) the nutritionally important RRR-α-tocopherol and/or 2 R, 4'-ambo, 8'-ambo-α-tocopherol contents; (iii) the amount of all-rac-α-tocopherol, all-rac-α-tocopheryl acetate, or all-rac-α-tocopheryl succinate fortified into the product. An accurate and precise chiral chromatographic method for the analysis of isomeric forms of α-tocopherol is described. The method is able to distinguish between natural and synthetic tocopherol sources. The method is accurate and precise and is suitable either for routine product compliance testing during product manufacture or as a possible reference method.