Routine Production Research Articles

Production of 67Cu at a biomedical cyclotron via 70Zn(p,α)67Cu reaction and its evaluation in a preclinical study using small animal SPECT/CT

Clinical advancements in nuclear medicine theranostics has excited a research interest in exploring novel radionuclides for medical use. The duo of the β- emitter 67Cu and the positron emitter 64Cu, has advantages over the well-established clinical pair 68Ga and 177Lu in terms of capability for high-precision therapy. Low availability has hindered the use of 67Cu whereas 64Cu has become established at a limited number of sites through production in low-to-medium energy biomedical cyclotrons. Via the reaction 70Zn(p,α)67Cu, 67Cu can also be cyclotron produced, although data on the cross sections of this reaction are sparse. Our aim in this study was three-fold: 1) to establish cross sections for relevant beam energies (14-16 MeV) of the 70Zn(p,α)67Cu reaction; 2) determine experimentally the thick target yield for 16.5 MeV proton beam; 3) establish a routine production of 67Cu for radiochemical and preclinical research. Additionally, our work aims to explore the feasibility of using biomedical cyclotrons for developing of novel therapeutic radionuclides.Thin layers of enriched 70Zn were electrodeposited onto silver foils to employ the stacked foils technique for assessing the cross section at six energies. The thick target yield was measured experimentally using a pressed [70Zn]ZnO target. Methods were developed for solid phase extraction separation of 67Cu from the target material, as well as quality control of the product with regards to radionuclidic and radiochemical purity. Radiolabelling of PSMA-617 precursor was performed and the end product injected in a healthy mouse for a kinetic study. As a proof of concept for preclinical applications The animal was then SPECT imaged using the 185 keV gamma emission line.Summarizing, our data confirm that biomedical cyclotrons can contribute in developing novel radionuclides, even of low cross section, for preclinical research.

Automated Production of [68Ga]Ga-Desferrioxamine B on Two Different Synthesis Platforms.

Background/Objectives: PET imaging of bacterial infection could potentially provide added benefits for patient care through non-invasive means. [68Ga]Ga-desferrioxamine B-a radiolabelled siderophore-shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa and sufficient serum stability for clinical application. In this report, we present data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette-based synthesis modules (Modular-Lab PharmTracer and GRP 3V) utilising commercially obtainable cassettes together with a licensed 68Ge/68Ga radionuclide generator. Methods: Quality control, including the determination of radiochemical purity, as well as a system suitability test, was set up via RP-HPLC on a C18 column. The two described production processes use an acetic acid/acetate buffer system with ascorbic acid as a radical scavenger for radiolabelling, yielding ready-to-use formulations with sufficient activity yield. Results: Batch data analysis demonstrated radiochemical purity of >95% by RP-HPLC combined with ITLC and excellent stability up to 2 h after synthesis. Specifications for routine production were set up and validated with four masterbatches for each synthesis module. Conclusions: Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable automated production of [68Ga]Ga-desferrioxamine B in-house with high reproducibility for clinical application.

Four Cases of Children With Phonological Impairment and Precocious Vocabulary: Making Sense of a Clinical Conundrum.

The purpose of this study was to describe the speech production, speech perception, vocabulary, and word learning abilities of lexically precocious 4-year-old children with phonological impairment, in an effort to better understand the underlying nature of phonological impairment in children. Using a case series approach, we identified four children with phonological impairment and precocious vocabulary abilities. Each child completed routine speech production and vocabulary assessments, as well as experimental speech perception and word learning tasks. The results from these tasks were then used to create profiles of each child's individual strengths and needs across the abilities assessed. Although all four children presented with phonological impairment and lexically precocious receptive and expressive vocabulary, they differed in their specific speech errors. One child presented with phonological speech errors only, while the other three children presented with an interdental lisp alongside their phonological errors. Three children presented with average speech perception abilities, and one child presented with poorer speech perception. The same three children also showed some learning of novel nonwords 1 week post-initial exposure, while the other child showed no evidence of word learning 1 week post-initial exposure. The clinical profiles of lexically precocious children with phonological impairment offered different insights into the nature of the problem. Although one child appeared to present with underspecified underlying representations of words, the other three children appeared to present with well-specified underlying representations. Of the three children with well-specified underlying representations, two appeared to have difficulty abstracting particular rules of the ambient phonological system. Further research is needed to improve our understanding of the underlying nature of phonological impairment. https://doi.org/10.23641/asha.26307640.

Development of high energy resolution crystal analyzers based on microporous ceramics for resonant inelastic x‐ray scattering program at High Energy Photon Source

AbstractThe spherically bent x‐ray crystal analyzer is one of the key optical elements for performing high energy resolution hard x‐ray spectroscopies based on Rowland circle geometry. To meet the requirements of Resonant Inelastic X‐ray Scattering (RIXS) program at High Energy Photon Source (HEPS), the fourth‐generation high energy synchrotron in Beijing, China, high energy resolution crystal analyzers were fabricated. The fabrication processes of vacuum‐mounted flat‐diced crystal analyzers using home‐designed devices with microporous ceramics are presented. The energy resolution of the vacuum‐mounted crystal analyzers, for measuring Cu K‐edge RIXS, is benchmarked with that of the glued flat‐diced crystal analyzers. Both the gluing and vacuum‐mounting are proven to be reliable techniques for the routine production of spherical bent diced crystal analyzers with energy resolution of tens of meV, and with good focal properties and efficiency. In particular, the vacuum‐mounted technique will be beneficial for the RIXS techniques to target multiple elements of interest.

"One Method to Label Them All": A Single Fully Automated Protocol for GMP-Compliant 68Ga Radiolabeling of PSMA-11, Transposable to PSMA-I&T and PSMA-617.

Prostate-specific membrane antigen (PSMA) is an ideal target for molecular imaging and targeted radionuclide therapy in prostate cancer. Consequently, various PSMA ligands were developed. Some of these molecules are functionalized with a chelator that can host radiometals, such as 68Ga for PET imaging. The 68Ga radiolabeling step benefits from process automation, making it more robust and reducing radiation exposure. To design a single automated radiolabeling protocol for the GMP-compliant preparation of [68Ga]Ga-PSMA-11, transposable to the production of [68Ga]Ga-PSMA-617 and [68Ga]Ga-PSMA-I&T. A GAIA® synthesis module and a GALLIAD® generator were used. Radio-TLC and radio-HPLC methods were validated for radiochemical purity (RCP) determination. Three [68Ga]Ga-PSMA-11 validation batches were produced and thoroughly tested for appearance and pH, radionuclide identity and purity, RCP, stability, residual solvent and sterility. Minimal modifications were made to the reagents and disposables for optimal application to other PSMA ligands. [68Ga]Ga-PSMA-11 for clinical application was produced in 27 min. The 3 validation batches met the quality criteria expected by the European Pharmacopoeia to allow routine production. For optimal transposition to PSMA-617, the solid phase extraction cartridge was changed to improve purification of the radiolabeled product. For application to PSMA-I&T, the buffer solution initially used was replaced by HEPES 2.7 M to achieve good radiochemical yields. Residual HEPES content was checked in the final product and was below the Ph. Eur. threshold. A single automated radiolabeling method on the GAIA® module was developed and implemented for 68Ga radiolabeling of 3 PSMA ligands, with slight adjustments for each molecule.

Analysis of Halal Literacy, Halal Awareness, Motivation and Religiousity of SMES on Interest in Halal Certification in Banjarmasin

Micro, Small, and Medium-Sized Enterprises (MSMEs) play a significant role in Banjarmasin City's local economic development. Along with this growth, halal products have great potential to gain the support of consumers whose awareness of halal products is increasing. Halal factors are becoming increasingly important to consumers when making routine product purchases. This study examines how the motivation,religiosity, halal literacy, and halal awareness of MSME (Micro, Small, and Medium Enterprises) actors affect their desire to get halal certification in Banjarmasin City. This study is conducted using field research using a quantitative descriptive technique. Purposive sampling, a non-probability sampling technique, selects samples based on the requirement to meet specific objectives, such as identifying MSMEs in Banjarmasin for a minimum of one year. A questionnaire is used for data collection, and the sample size is 96. Using SPSS 25.0 for Windows applications,the following data analysis procedures were employed: hypothesis testing, data validity analysis, and descriptive data analysis. The findings indicate that MSMEs' interest in Halal Certification in Banjarmasin City is significantly influenced, at least in part, by the factors of Halal Literacy, Halal Awareness, Motivation, and Religiosity. The factors significantly impacting MSMEs' interest in halal certification in Banjarmasin City simultaneously include motivation,religiosity, halal literacy, and halal awareness.

Development of a versatile [68Ga]Ga-FAPI-46 automated synthesis suitable to multi-elutions of germanium-68/gallium-68 generators.

Gallium-68-labeled FAPI-46 has recently been proposed as a novel positron emission tomography imaging probe to diagnose and monitor a wide variety of cancers. Promising results from several ongoing clinical trials have led to a soaring demand for this radiotracer. Typical [68Ga]Ga-FAPI-46 labeling protocols do not cope with multiple generator elutions, leaving radiopharmacies unable to scale-up the production and meet the demand. Here, we propose a robust and efficient automated radiosynthesis of [68Ga]Ga-FAPI-46 on the Trasis miniAllinOne synthesizer, featuring a prepurification step which allows multiple generator elutions and ensures compatibility with a wide range of gallium-68 generators. Our approach was to optimize the prepurification step by first testing five different cationic cartridge chemistries. Only the strong cationic exchange (SCX) cartridges tested had sufficient affinities for quantitative trapping of >99.9%, while the weak cationics did not exceed 50%. Packaging, rinsing, or flowing of the selected SCX cartridges was not noticeable, but improvements in fluidics managed to save time. Based on our previous development experience of [68Ga]Ga-FAPI-46, radiolabeling optimization was also carried out at different temperatures during 10min. At temperatures above 100°C, radiochemical yield (RCY) > 80% was achieved without significantly increasing the chemical impurities (<5.5μgmL-1). The optimized sequence was reproducibly conducted with three different brands of widely used generators (RCY >88%). A comparison with radiosyntheses carried out without prepurification steps was also conclusive in terms of RCY, radiochemical yield, and chemical purity. Finally, high-activity tests using elutions from three generators were also successful for these parameters. [68Ga]Ga-FAPI-46 was consistently obtained in good radiochemical yields (>89%, n = 3), and the final product quality was compliant with internal specifications based on European Pharmacopoeia. This process is suitable for GMP production and allows scaling-up of routine productions, higher throughput, and, ultimately, better patient care.

Utility of an in-line somatic cell count sensor for selecting cows for dry-cow therapy

Minimizing the use of antimicrobials at the end of lactation (dry cow therapy, DCT) requires categorization of cows as likely infected or uninfected. While microbiology is the gold standard for such categorization, the costs of doing so mean that indirect tests such as somatic cell count (SCC) are commonly used. An in-line SCC sensor (SenseHub In Line Somatic Cell Count, in-line SCC) is commercially available but its utility to differentiate cows eligible for dry cow therapy has not been assessed. This prospective diagnostic accuracy study was undertaken to define the sensitivity (Se) and specificity (Sp) of SenseHub SCC against cow-composite milk samples submitted for conventional microbiology. A secondary objective was to assess the utility of SenseHub SCC compared with the maximum (max DHI SCC) or last (last DHI SCC) SCC determined from cow-composite milk samples collected as part of routine herd production recording at monthly intervals throughout lactation. Cows (n = 1,544) from 4 spring-calving, predominantly pasture-fed dairy herds from 3 regions of New Zealand had cow-composite milk samples collected following aseptic teat end preparation immediately before or after the final milking of lactation. These samples were submitted for routine microbiology. The microbiology data from approximately half the cows (n = 770; training data set) were randomly selected after blocking for intramammary infection (IMI) status within herd and these data were used to determine the optimal predictor for indicating IMI from the in-line SCC data by maximizing the area under the receiver operator curve (AUC). The average of the in-line SCC over the final 12 weeks of lactation (in-line 12wSCC) was found to be the best predictor and used for further analyses. The Se and Sp of the in-line SCC for any IMI or for a major pathogen IMI (defined as presence of Staphylococcus aureus, Streptococcus dysgalactiae or Streptococcus uberis) was calculated using the test data set (n = 774). The AUC for the maximum and last DHI SCC were compared with that of the in-line 12wSCC. The cow-level prevalence of any IMI or a major IMI across the entire population was 50.6% and 14.2%, respectively. At a cutpoint of 150,000 cells/mL, Se and Sp of the in-line 12wSCC for any IMI was 0.68 (95%CI 0.64-0.72) and 0.71 (95% CI 0.65-76), respectively, and the Se and Sp for a major pathogen IMI was 0.89 (95%CI 0.82-0.95) and 0.51 (95% CI 0.47-0.55), respectively. The AUC for a major pathogen IMI was 0.82 (95% CI 0.79-0.86), 0.82 (95% CI 0.78-0.86) and 0.84 (95% CI 0.90-0.97) for in-line 12wSCC, max DHI SCC and last DHI SCC, respectively. These AUC did not differ and the AUC for the in-line 12wSCC was non-inferior to that of the last and maximum HT SCC (both P < 0.001). It was concluded that the in-line 12wSCC had an AUC, Se and Sp not different from DHI SCC data and hence this test has utility in selecting cows for different dry cow therapy treatments.

A birchbark anthropomorphic article from the Early Iron Age Novotroitskoye necropolis in the Upper Ob

This paper discusses a burial doll discovered within the Early Iron Age necropolis of Novotriotskoye-1 during field research by the expedition of Barnaul State Pedagogical Institute under the direction of A.P. Umanskii in the Talmensky District of Altai Krai. The object found in a woman's burial is an anthropomorphic image with wing-shaped arms and schematically indicated facial features, namely prominent eyes, eyebrows, nose and gouged mouth. The purpose of this work is to publish the Novotriotskoye idol in high quality, since in various publications by A.P. Umanskii and co-authors it was presented only in schematic drawings. Cleaning the object from field dirt, undertaken by the authors, made it possible to better observe the stylistic features of the artifact. Furthermore, the authors made an attempt to create experimental stylistic replicas of the analysed article. Three scenarios of its production have been implemented, and the details are presented in this publication. The authors suggest that the schematic exterior of the Novotriotskoye object allows considering it as a peculiar burial doll. The iconography of the Novotriotskoye anthropomorphic image has been characterized in the context of connections of the Upper Ob River region population of the second half of the 1st mil. AD with the cultures of Northern Asia (Tashtyk, Kokel, “Bulan-Koby”). A wide range of archaeological and ethnographic parallels to the discussed anthropomorphic ob-ject has been analyzed. The authors conclude that the routine production of anthropomorphic images and masks was deeply rooted in the Ob River region, and it appeared in the Early Iron Age. Earlier, we came across an opin-ion, that its origins need to be searched for among the cultures of Southern Siberia — mainly Khakass-Munusinsk Basin and Eastern Siberia. The discovery of the studied birchbark image in the Novotriotskoye necropolis in-cludes the Upper Ob River region into the potential areas of formation of this tradition.

Improved Radiosynthesis and Automation of [11C]2-(2,6-Difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2) for Positron Emission Tomography of the Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptor.

A new automated radiosynthesis of [11C]2-(2,6-difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2), a radiopharmaceutical for the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production of larger batches of [11C]K2 for (pre)clinical PET imaging applications. To meet demands for the imaging agent from our functional neuroimaging collaborators, herein, we report a current good manufacturing practice (cGMP)-compliant synthesis of [11C]K2 using a commercial synthesis module. The new synthesis is fully automated and has been validated for clinical use. The total synthesis time is 33 min from end of bombardment, and the production method provides 2.66 ± 0.3 GBq (71.9 ± 8.6 mCi) of [11C]K2 in 97.7 ± 0.5% radiochemical purity and 754.1 ± 231.5 TBq/mmol (20,382.7 ± 6256.1 Ci/mmol) molar activity (n = 3). Batches passed all requisite quality control testing confirming suitability for clinical use.

Optimised production of technetium-94m for PET imaging by proton-irradiation of phosphomolybdic acid in cyclotron liquid target

Natural-abundance phosphomolybdic acid (H3(Mo12PO40) ‧12H2O, 0.181–0.552 g Mo/mL) solutions were irradiated with 12.9 MeV protons on a GE PETtrace cyclotron using an adapted standard liquid target. Technetium-94m (94mTc) was produced through the 94Mo(p,n)94mTc nuclear reaction with saturation yields of up to 53 ± 6 MBq/μA. End of bombardment activities of 161 ± 17 MBq and 157 ± 7 MBq were achieved for the 0.552 g Mo/mL solution (10 μA for 30 min) and 0.181 g Mo/mL solution (15 μA for 60 min), respectively. No visible degradation of the niobium target body and foil were seen during the irradiations of up to 15 μA for 60 min. The produced 94mTc was separated from the target phosphomolybdic acid solution with >98% recovery using an aqueous biphasic extraction resin. Compared to previous reported liquid target methods for 94mTc production, the better production yield, in-target solution stability during irradiation and 94mTc separation recovery of phosphomolybdic acid makes it a very promising target material for routine clinical 94mTc production at medical facilities with liquid targets already installed for 18F production.

Implementation Of The CSR Program Of PT Pertamina Patra Niaga Fuel Terminal Rewulu In Improving The Capacity Of Local Food Utilization Of Koro Beans

Many local food commodities in Indonesia, especially Yogyakarta, are still not utilized into products that are worth selling. This results in the amount continuing to increase in fresh conditions, resulting in a short shelf life. For this reason, through the implementation of the CSR program Pertamina Patra Niaga Fuel Terminal Rewulu together with the academic team aims to 1) increase the use of local food, especially jack beans which are easy to grow in all areas in Bantul, Yogyakarta, 2) Prepare the abilities of members of the Women's Farmers Group (KWT) to be able to process milk from koro beans. The assistance methods used are in the form of socialization, discussion, training and assistance in processing dairy products, as well as evaluation. This activity was carried out in several meetings to ensure that KWT members were able to carry out the processing appropriately. Based on the results of observations, it was found that KWT members were able to practice the training provided and carry out routine production activities during the last three months during the monitoring and evaluation period. It is hoped that through this mentoring activity, KWT members can take advantage of local food which is available in abundance with a higher selling value.

Niobium as Preferential Material for Cyclotron Target Windows

The present work promotes and validates the benefits of using niobium instead of Havar® as the material for the target windows in most routine irradiations in cyclotrons. Calculation of the material activation and measurements of the contamination of the transferred target liquids show major improvements with the use of niobium. Also, the data of the daily routine productions at our production center are presented, proving that Havar® is not mandatory unless large target currents and/or pressures are required.

Skin care habits of patients with eczema at Kiambu Level 5 Hospital, Kiambu county, Kenya: A retrospective cross-sectional study

BackgroundThere is a dearth of data on eczema from the African continent despite the purported increasing burden. ObjectivesTo describe the prevalence of eczema at Kiambu Level 5 Hospital and patient skincare. MethodsA descriptive retrospective cross-sectional research design was used describing the period between 2016 and 2020. Data analysis was done using STATA Version 13. Geo spatial mapping of patient residence was also done. ResultsEczema was the most common skin condition diagnosed with a prevalence of 25.5%. Majority of the patients favoured the use of non-conventional products such as bar soap and milking jelly as routine skincare products. Geospatial mapping demonstrated a higher prevalence of eczema in the urban areas and also revealed access to a specialist as a contributor to health-seeking behaviour. LimitationsSubtypes of eczema were not described and this data only reflects one facility serving an entire county. ConclusionThe prevalence of eczema in KL5H mirrors the increasing global burden of eczema and that Kenya is not exempted from the affliction of eczema. Urban environments have a higher density of eczema in Kiambu. More research is needed to decipher the impact of the preferred non-conventional skin care products on eczema.

A protocol for controlled reactivity shift in the 2,2-difluorovinyl motif used for selective S-18F and C-18F bond formation.

Positron emission tomography (PET) is a powerful imaging technique for biomedical research, drug development and medical diagnosis. The power of PET lies in biochemically selective radiotracers, labelled with positron emitters like fluorine-18 image chemical processes in vivo. A rapid and remarkably efficient, unprecedented protocol to select between S-F and C-F bond formation based on activation of 1,1-difluoroethylene groups followed by selective oxidation or reduction is described. While transition metal mediated conditions can be employed, the reaction proceeds in high yield using unobjectionable chemical reagents amenable to routine radiotracer production. The latter bodes well for facile clinical translation of the method. The new technique affords radiotracers and the labelling reagent 2,2-difluoro-2-(fluoro-18F)ethyl 4-methylbenzenesulfonate ([18F]1b) in excellent yield. Following oxygenation of the reaction mixture with medical oxygen or air, sulfonyl fluorides are obtained as the primary product. The new protocol was employed in a proof of principle to develop a radiometric assay for quantitation of sulfonylation yield with sulfonyl fluoride reagents. With operational ease and mild conditions, the method bodes a high potential for radiolabelling of biomolecules, known enzyme inhibitors and other temperature-sensitive compounds.

Technological aspects of developing drugs in the form of transmucosal and dispersible films

The creation of new forms of drugs is one of the most important areas of development of the modern pharmaceutical industry. Orodispersible films have a number of advantages over conventional tablets and injections. Developing and scaling technology is time-consuming, resource-intensive, and expensive. The determination of critical parameters affecting the technology and quality of the finished product minimizes the risks of obtaining negative results during implementation and routine industrial production. The work presents the studies of the influence of excipients in the formulation on the characteristics of the dosage form and the technological process. The approach to development was considered from the standpoint of choosing a qualitative composition of the drug. The experiments were aimed at determining the most suitable viscosity of hydroxypropyl methylcellulose (HPMC), which makes up the matrix of the dosage form; optimal polymer- plasticizer ratios have been established. The studies carried out are basic in the creation of a transmucosal dosage form and orodispersible films and make it possible to optimize the process of developing the dosage form and reduce risks during the transfer of technology to production.

Efficient scar-free knock-ins of several kilobases in plants by engineered CRISPR-Cas endonucleases

In plants and mammals, non-homologous end-joining is the dominant pathway to repair DNA double-strand breaks, making it challenging to generate knock-in events. In this study, we identified two groups of exonucleases from the herpes virus and the bacteriophage T7 families that conferred an up to 38-fold increase in homology-directed repair frequencies when fused to Cas9/Cas12a in a tobacco mosaic virus-based transient assay in Nicotiana benthamiana. We achieved precise and scar-free insertion of several kilobases of DNA both in transient and stable transformation systems. In Arabidopsis thaliana, fusion of Cas9 to a herpes virus family exonuclease led to 10-fold higher frequencies of knock-ins in the first generation of transformants. In addition, we demonstrated stable and heritable knock-ins in wheat in 1% of the primary transformants. Taken together, our results open perspectives for the routine production of heritable knock-in and gene replacement events in plants.

Continuous Production of Ethylene and Hydrogen Peroxide from Paired Electrochemical Carbon Dioxide Reduction and Water Oxidation

AbstractPaired electrolysis offers an auspicious strategy for the generation of high‐value chemicals, at both the anode and cathode, in an integrated electrochemical reactor. Through efficient electron utilization, routine product misuse at overlooked electrodes can be prevented. Here, an original paired electrosynthetic system is reported that can convert CO2 to ethylene (C2H4) at the cathode, and water to hydrogen peroxide (H2O2) at the anode under a single pass of electric charge. Amongst various investigated copper (Cu) nanomorphologies, the bespoke mixed Cu nanowire/nanoparticle catalyst recorded a peak C2H4 Faraday efficiency (FE) of 60% following 370 h of electrolysis at 200 mA cm−2, while the tailored boron‐doped diamond (BDD) anode accumulated an unprecedented ≈1% w/w of H2O2 in 4 m K2CO3 upon applying 300 mA cm−2 for 10 h. When paired, the dual C2H4‐H2O2 electrochemical cell attains a combined FE of 120% for 50 h at 200 mA cm−2, a combined energy efficiency (EE) of 69%, and a 50% decrease in the overall electrical energy consumption (EEC) compared to the individual electrosynthesis of C2H4 and H2O2.

On the local aspect of valley magnetic moments

Valley magnetic moments play a crucial role in valleytronics in 2D hexagonal materials. Traditionally, insights drawn from the study of quantum states in homogeneous bulks have led to a widespread belief that only materials with broken structural inversion symmetry can exhibit nonvanishing valley magnetic moments. This belief, however, limits the scope of relevant applications, especially for materials with inversion symmetry, such as gapless monolayer graphene, despite its advantage in routine growth and production. This work revisits valley-derived magnetic moments in a broad context covering inhomogeneous structures as well. It generalizes the notion of a valley magnetic moment for a state from an integrated quantity to the local field called the “local valley magnetic moment” with space-varying distribution. It explores the local magnetic moment analytically both within the Dirac model and through a symmetry argument. Numerical investigations are conducted within the tight-binding model. Overall, we demonstrate that the breaking of inversion symmetry in the electron probability distribution leads to nonvanishing local magnetic moments. This probability-based breaking can occur in both structural inversion symmetric and symmetry-broken structures. In suitable inversion-symmetric structures with inhomogeneity, e.g., zigzag nanoribbons of gapless monolayer graphene, it is shown that the local moment of a state can be nonvanishing while the corresponding integrated moment is subject to the broken symmetry constraint. Moreover, it is demonstrated that the local moment can interact with space-dependent magnetic fields, resulting in field effects such as valley Zeeman splitting. Such effects can be exploited for local valley control as a conduit for the implementation of valleytronics.

Optimization and automation of the radiosynthesis of [18F]Lu-LuFL as a clinically useful PET ligand targeting FAP for tumor imaging

Recently, a novel radiohybrid tracer [18F]Lu-LuFL targeting the fibroblast activation protein (FAP) has been developed for PET imaging of solid tumors. This tracer has shown promising results, prompting us to conduct a first-in-human study to evaluate its efficacy for PET imaging of FAP in human body. In order to facilitate the routine production and clinical application of [18F]Lu-LuFL, a straightforward and efficient automated synthesis is described. The optimum labeling parameters were determined at laboratory scale, and subsequently incorporated into an automated production process. Further studies have demonstrated that clinical doses of [18F]Lu-LuFL can be prepared within 19 min, with excellent radio chemical purity (>99%) and activity yield (23.58% ± 2.20%, non-decay corrected), coupled with solid phase extraction (SPE) purification method. All the quality control results satisfy the required criteria for release. In conclusion, we have successfully synthesized [18F]Lu-LuFL with sufficient radioactivity and superior quality, thereby establishing its potential for further clinical application.