Cyclotron (Netherlands)

The 18 kDa translocator protein (TSPO) is a critical target for PET imaging of neuroinflammation in central nervous system (CNS) disorders; however, many clinical TSPO PET tracers are limited by sensitivity to rs6971 polymorphism. In this study, three novel fluorine-containing oxypropanamide ligands were developed, with 11 (LW1, Ki = 0.07 nM) and 12 (LW2, Ki = 0.05 nM) showing high TSPO affinity. The radiolabeled [18F]12 demonstrated superior metabolic stability, specificity, and reduced polymorphism sensitivity compared to [18F]11 in autoradiography using Tg2576, PS19 mouse models, and human brain tissues. [18F]12 was further evaluated in APP/PS1 transgenic mice and ischemic stroke rats for neuroinflammatory imaging and in healthy rhesus monkeys to access pharmacokinetics via dynamic PET with arterial sampling. The combination of excellent brain penetration, high specificity, and rs6971 insensitivity supports [18F]12 as a promising TSPO PET tracer for clinical translation.

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

Electrochemical conversion of CO2 and H2O to fuels and chemicals provides a promising approach to simultaneously mitigate greenhouse emission and store surplus energy, which reduces electricity network variation due to increased intermittent renewable energy (such as solar and wind) utilization. Metal supported solid oxide electrolyzers (MS-SOEs) developed at Lawrence Berkeley National Laboratory provide advantages of rapid start-up, mechanical ruggedness, redox tolerance, dynamic operation, and low-cost materials. A relatively high operating temperature range of 600 to 750°C promotes energy efficiency and allows utilization of thermal energy such as steam.In this work, efficient and stable catalysts developed at the University of South Carolina have been infiltrated in the symmetrical and porous MS-SOE architecture. The phase purity has been analyzed by X-day diffraction. The morphologies of these infiltrated and posttest catalysts have been examined by scanning electron microscopy. Optimization of cell structure, processing temperature, cell voltage, and catalyst infiltration cycles for better cell performance will be presented. The stability of MS-SOEs has been evaluated during continuous operation for >200 hours. The cell degradation mechanisms revealed by electrochemical impedance spectroscopy and high-resolution scanning electron microscopy techniques will be presented.In addition to pure CO2 electrochemical conversion, effects of additional water and hydrogen in CO2 feedstock will be analyzed. Faradic efficiency and chemical selectivity calculated from gas chromatograph and electrochemical analyses will be presented.

ABSTRACTIncreases in sequencing capacity, combined with rapid accumulation of publications and associated data resources, have increased the complexity of maintaining associations between literature and genomic data. As the volume of literature and data have exceeded the capacity of manual curation, automated approaches to maintaining and confirming associations among these resources have become necessary. Here we present the Data Citation Explorer (DCE), which discovers literature incorporating genomic data whether or not provenance was clearly indicated. This service provides advantages over manual curation methods including consistent resource coverage, metadata enrichment, documentation of new use cases, and identification of conflicting metadata. The service reduces labor costs associated with manual review, improves the quality of genome metadata maintained by the U.S. Department of Energy Joint Genome Institute (JGI), and increases the number of known publications that incorporate its data products. The DCE facilitates an understanding of JGI impact, improves credit attribution for data generators, and can encourage data sharing by allowing scientists to see how reuse amplifies the impact of their original studies.

This study aims to develop high-capacity hard carbon anode materials for alkali-ion batteries by controlling the microstructures of non-graphitic hard carbon through an annealing protocol and investigating the effects on the alkali-ion storage mechanisms using physical, chemical, and electrochemical analytical techniques. The hard carbon materials were synthesized at temperatures ranging from 900 °C to 1600 °C. Those synthesized at 1100 °C with high surface area and abundant defects exhibited the highest reversible capacity in Li- and K-ion systems, with the storage dominated by surface-adsorption mechanisms. In contrast, the hard carbon compounds prepared at 1400 °C with numerous curve-featured pores delivered the highest reversible capacity in the Na-ion system, indicating that these pores are the preferred Na-ion storage sites, particularly in low-voltage plateau regions. This study provides a comprehensive understanding of the relationship between microstructures and alkali-ion storage mechanisms in non-graphitic hard carbon and highlights the importance of tailoring the microstructures of hard carbon to achieve high specific capacity for the desired alkali-ion species.

Objective. Proton therapy experiments in small animals are useful not only for pre-clinical and translational studies, but also for the development of advanced technologies for high-precision proton therapy. While treatment planning for proton therapy is currently based on the stopping power of protons relative to water (i.e. the relative stopping power (RSP)), estimated by converting the CT number into RSP (Hounsfield unit (HU)-RSP conversion) in reconstructed x-ray computed tomography (XCT) images, the HU-RSP conversion causes uncertainties in RSP, which affect the accuracy of dose simulation in patients. Proton computed tomography (pCT) has attracted a great deal of attention due to its potential to reduce RSP uncertainties in clinical treatment planning. However, as the proton energies for irradiating small animals are much lower than those used clinically, the energy dependence of RSP may negatively affect pCT-based RSP evaluation. Here, we explored whether the low-energy pCT approach provided more accurate RSPs when planning proton therapy treatment for small animals. Approach. We evaluated the RSPs of 10 water- and tissue-equivalent materials with known constituent elements based on pCT measurements conducted at 73.6 MeV, then compared them with XCT-based and calculated RSPs to investigate energy dependence and achieve more accurate RSPs for treatment planning in small animals. Main results. Despite the low proton energy, the pCT approach for RSP evaluation yields a smaller root mean square deviation (1.9%) of RSP from the theoretical prediction, compared to conventional HU-RSP conversion with XCT (6.1%). Significance. Low-energy pCT is expected to improve the accuracy of proton therapy treatment planning in pre-clinical studies of small animals if the RSP variation that can be attributed to energy dependence is identical to the variation in the clinical proton energy region.

PurposeThis study aimed to investigate functional abnormalities in the brain of patients with neurological adverse effects following COVID-19 (coronavirus disease 2019) vaccination using 18F-FDG PET/MRI and 15O-water PET.MethodsEight patients (1 man and 7 women, aged 26–47 years [median age, 36.5 years]) who experienced neurological symptoms after the first COVID-19 vaccination underwent CT, MRI, 18F-FDG PET/MRI, and 15O-water PET of the brain. After 7 days, each patient underwent a follow-up 18F-FDG PET/MRI and 15O-water PET of the brain. Imaging data were analyzed using visual and semiquantitative analyses, which included a cluster subtraction workflow (P = 0.05).ResultsThere was no evidence of vascular abnormalities, acute infarction, or hemorrhage on the CT or MRI scans. On the 15O-water PET images, 1 patient had mildly significant decreases in perfusion in the bilateral thalamus and bilateral cerebellum, and another patient showed a diffuse increase in perfusion in the cerebral white matter. The visual and semiquantitative analyses showed hypometabolism in the bilateral parietal lobes in all 8 patients on both the first and follow-up 18F-FDG PET/MRI scans. Metabolic changes in the bilateral cuneus were also observed during the first visit; all patients exhibited neurological symptoms. Moreover, 6 patients showed hypometabolism, and 2 patients showed hypermetabolism.ConclusionAll regions of metabolic abnormality were part of the fear network model that has been implicated in anxiety. Our study findings support the concepts of and provide evidence for the immunization stress-related response and the biopsychosocial model.

Astrocytes support the health of the brain, but reactive astrocytes are strongly associated with various neurodegenerative diseases., including the neurotoxic A1 astrocyte and neuroprotective A2 astrocyte, and an increase in their density has been demonstrated in Alzheimer’s disease brains. Positron-emission tomography (PET) is a nuclear imaging technique, making it possible to follow-up changes in astrocytic activation in vivo, thereby tracing disease progression. Monoamine oxidase B (MAO-B) is one of the markers for imaging astrocytes, whose activity is expressed in plaque-associated astrocytes. Recently, we developed a selective and reversible tracer for MAO-B called [18F]SMBT-1. Besides, [3H]BU99008 is a tracer designed for another astrocyte marker called imidazoline 2 binding sites (I2BS). Therefore, the aim of this study was to characterize which phenotype of astrocyte dose MAO-B exist in and whether [18F]SMBT-1 can be used for imaging astrocytes.