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LC-MS Supported Studies on the in Vitro Metabolism of both Enantiomers of Flubatine and the in Vivo Metabolism of (+)-[18F]Flubatine—A Positron Emission Tomography Radioligand for Imaging α4β2 Nicotinic Acetylcholine Receptors
摘要： Both enantiomers of [18F]flubatine are promising radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). To support clinical studies in patients with early Alzheimer’s disease, a detailed examination of the metabolism in vitro and in vivo has been performed. (+)- and (?)-flubatine, respectively, were incubated with liver microsomes from mouse and human in the presence of NADPH (β-nicotinamide adenine dinucleotide 2′-phosphate reduced tetrasodium salt). Phase I in vitro metabolites were detected and their structures elucidated by LC-MS/MS (liquid chromatography-tandem mass spectrometry). Selected metabolite candidates were synthesized and investigated for structural confirmation. Besides a high level of in vitro stability, the microsomal incubations revealed some species differences as well as enantiomer discrimination with regard to the formation of monohydroxylated products, which was identified as the main metabolic pathway in this assay. Furthermore, after injection of 250 MBq (+)-[18F]flubatine (specific activity > 350 GBq/μmol) into mouse, samples were prepared from brain, liver, plasma, and urine after 30 min and investigated by radio-HPLC (high performance liquid chromatography with radioactivity detection). For structure elucidation of the radiometabolites of (+)-[18F]flubatine formed in vivo, identical chromatographic conditions were applied to LC-MS/MS and radio-HPLC to compare samples obtained in vitro and in vivo. By this correlation approach, we assigned three of four main in vivo radiometabolites to products that are exclusively C- or N-hydroxylated at the azabicyclic ring system of the parent molecule.
关键词： epibatidine,liquid chromatography-mass spectrometry (LC-MS),flubatine,NCFHEB,liver microsomes,nicotinic acetylcholine receptors (nAChRs),radiometabolites,positron emission tomography (PET)
更新于2025-09-04 15:30:14
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Evaluation of LFS continuous scintillation crystals for PET
摘要： The suitability of monolithic Lutetium Fine Silicate (LFS) continuous scintillation crystals coupled to 64-channel SiPM-TSV matrices for small animal PET has been evaluated. Three crystals of size 25.8×25.8×15 mm3 were tested: LYSO white coating, LFS white coating (LFS-W) and LFS specular coating (LFS-S). Electronically collimated measurements were carried out to compare the performance of LYSO and LFS crystals. Mean energy resolutions of 14%, 17% and 19% were measured for LYSO, LFS-S and LFS-W respectively. Similar intrinsic spatial resolutions were found for all three crystals in the central region. Different versions of the light model used to estimate the interaction position of the photons in the detector have been studied. Further measurements with two detector heads of each crystal type in coincidence have also been carried out with a moveable 22Na source. A ML-MLEM image reconstruction code is used to reconstruct the data. Final position resolutions for all three configurations show similar values. Taking into account that LYSO and LFS present similar performance levels (and considering that LFS has better timing resolution than LYSO) we conclude that LFS is a valid substitute for LYSO.
关键词： Continuous scintillation crystals,LFS,PET,Resolution,SiPM,ML-MLEM,LYSO
更新于2025-09-04 15:30:14
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Towards More Structure: Comparing TNM Staging Completeness and Processing Time of Text-Based Reports versus Fully Segmented and Annotated PET/CT Data of Non-Small-Cell Lung Cancer
摘要： Results of PET/CT examinations are communicated as text-based reports which are frequently not fully structured. Incomplete or missing staging information can be a significant source of staging and treatment errors. We compared standard text-based reports to a manual full 3D-segmentation-based approach with respect to TNM completeness and processing time. TNM information was extracted retrospectively from 395 reports. Moreover, the RIS time stamps of these reports were analyzed. 2995 lesions using a set of 41 classification labels (TNM features + location) were manually segmented on the corresponding image data. Information content and processing time of reports and segmentations were compared using descriptive statistics and modelling. The TNM/UICC stage was mentioned explicitly in only 6% (n=22) of the text-based reports. In 22% (n=86), information was incomplete, most frequently affecting T stage (19%, n=74), followed by N stage (6%, n=22) and M stage (2%, n=9). Full NSCLC-lesion segmentation required a median time of 13.3 min, while the median of the shortest estimator of the text-based reporting time (R1) was 18.1 min (p<0.001), lesion size (p<0.001) correlated significantly with the segmentation time, but not with the estimators of text-based reporting time. Numerous text-based reports are lacking staging information. A segmentation-based reporting approach tailored to the staging task improves report quality with manageable processing time and helps to avoid erroneous therapy decisions based on incomplete reports. Furthermore, segmented data may be used for multimedia enhancement and automatization.
关键词： segmentation,TNM staging,structured reporting,NSCLC,PET/CT
更新于2025-09-04 15:30:14
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Room-temperature RF magnetron sputtering deposition of hydrogenated Ga-doped ZnO thin films on PET substrates for PDLC devices
摘要： In this work, hydrogenated gallium-doped zinc oxide (HGZO) thin films were deposited on polyethylene terephthalate substrates at room temperature by RF magnetron sputtering. The effects of RF power and Ar + H2 flow rate on electrical and optical properties of HGZO thin films were investigated systematically. All of HGZO thin films exhibited a high average transmittance of about 77.3–82.9% in the visible range, and the minimum resistivity value reached 7.1 × 10?4 ?·cm. Potential application of polymer-dispersed liquid crystal device based on HGZO thin film was also successfully demonstrated.
关键词： RF magnetron sputtering,HGZO thin films,PDLC devices,PET substrates
更新于2025-09-04 15:30:14
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[Institution of Engineering and Technology 12th European Conference on Antennas and Propagation (EuCAP 2018) - London, UK (9-13 April 2018)] 12th European Conference on Antennas and Propagation (EuCAP 2018) - Transparent and Flexible V-Shaped Antenna for 5G Wireless Applications
摘要： This paper demonstrates the design of transparent and flexible coplanar waveguide fed (CPW) antennas operating from 23 GHz to 29.5 GHz, covering the necessary frequency bands for 5G wireless communications. A Y-shaped antenna is modelled using AgHT transparent conductive material over Polyethylene Terephthalate (PET) substrate to achieve conformity. Then the Y shaped structure has been transformed to T shape, by changing the angle between the arms of the antenna. The consequent change in frequency, gain and radiation pattern has been demonstrated. The simulated results of the proposed antenna show that this antenna is well suited for future 5G applications because of its transparency, flexibility, light-weight and wide achievable frequency bandwidth near mmWave frequency band.
关键词： PET substrate,5G communications,Transparent antenna,Flexible antenna,AgHT material
更新于2025-09-04 15:30:14
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Metabolic Volumetric Parameters in <sup>11</sup> C-Choline PET/MR Are Superior PET Imaging Biomarkers for Primary High-Risk Prostate Cancer
摘要： Purpose. Positron emission tomography/magnetic resonance imaging (PET/MRI) can facilitate the use of noninvasive imaging biomarkers in clinical prostate cancer staging. Although multiparametric MRI is a widely used technique, the clinical value of simultaneous PET imaging remains unclear. This study aimed at investigating this issue. Methods. Between January 2015 and December 2016, 31 high-risk prostate cancer patients underwent 11C-choline PET/MRI for staging purposes. Clinical characteristics and imaging parameters, including the standardized uptake value (SUV) and metabolic volumetric parameters from PET imaging; apparent diffusion coefficient (ADC) values from diffusion-weighted imaging; and volume transfer rate constant (Ktrans), reflux rate constant (Kep), and initial area under curve (iAUC) in 60 seconds from dynamic contrast-enhanced (DCE) MRI were analyzed. Results. 11C-Choline PET imaging parameters were significantly correlated with prostate-specific antigen (PSA) levels, and metabolic volumetric parameters, including metabolic tumor volume (MTV) and uptake volume product (UVP), showed significant correlations with other MRI parameters. In our cohort analysis, the PET/MRI parameters UVP/minimal ADC value (ADCmin) and kurtosis of Kep (Kepkur)/ADCmin were significant predictors for progression-free survival (PFS) (HR = 1.01, 95% CI: 1.00–1.02, p = 0.031 and HR = 1.09, 95% CI: 1.02–1.16, p = 0.009, respectively) in multivariate Cox regression analysis. High UVP/ADCmin and Kepkur/ADCmin values were significantly associated with shorter PFS. Conclusions. Metabolic volumetric parameters such as MTV and UVP can be routinely used as PET imaging biomarkers to add prognostic value and show better correlations in combination with MR imaging parameters in high-risk prostate cancer patients undergoing 11C-choline PET/MRI.
关键词： 11C-choline,metabolic volumetric parameters,imaging biomarkers,PET/MRI,prostate cancer
更新于2025-09-04 15:30:14
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Quantitative Analysis of <sup>18</sup> F-PF-06684511, a Novel PET Radioligand for Selective β-secretase 1 Imaging, in Non-human Primate Brain
摘要： Beta-secretase 1 (BACE1) is a key enzyme in the generation of beta-amyloid, which is accumulated in the brain of Alzheimer’s disease (AD) patients. PF-06684511 was identified as a candidate PET ligand for imaging BACE1 in the brain, and showed high specific binding in an initial assessment in a non-human primate (NHP) PET study utilizing 18F-PF-06684511. In this effort, we aimed to quantitatively evaluate the regional brain distribution of 18F-PF-06684511 in NHPs under baseline and blocking conditions as well as assess the target occupancy of BACE1 inhibitors. In addition, NHP whole body PET measurements were performed to estimate the effective radiation dose. Methods: Initial brain PET measurements were performed at baseline and after oral administration of 5 mg/kg of LY2886721, a BACE1 inhibitor, in two cynomolgus monkeys. Kinetic analysis was performed with the radiometabolite-corrected plasma input function. In addition, a wide dose range of another BACE1 inhibitor, PF-06663195, was examined to investigate the relationship between the brain target occupancy and plasma concentration of the drug. Finally, the effective radiation dose of 18F-PF-06684511 was estimated based on the whole body PET measurements in NHPs. Results: Radiolabeling was accomplished successfully with an incorporation radiochemical yield of 4-12% (decay corrected) from fluorine-18 ion. The radiochemical purity was greater than 99%. The whole brain uptake of 18F-PF-06684511 reached peak (approximately 220%SUV) at approximately 20 minutes and decreased thereafter (approximately 100%SUV at 180 minutes). Two-tissue compartment model described the time activity curves well. Pre-treatment with LY2886721 reduced the total distribution volume of 18F-PF-06684511 by 48 – 80% depending on the brain regions, confirming its in vivo specificity. BACE1 occupancy of PF-06663195, estimated using Lassen occupancy plot, showed a dose-dependent increase. The effective dose of 18F-PF-06684511 was 0.043 mSv/MBq for humans. Conclusion: 18F-PF-06684511 is the first successful PET radioligand for BACE1 brain imaging that demonstrates favorable in vivo binding and brain kinetics in NHPs. (306/350 words)
关键词： PET,brain,BACE1,occupancy,radiation dose,non-human primate
更新于2025-09-04 15:30:14
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Dual-ended readout small animal PET detector by using 0.5?mm pixelated LYSO crystal arrays and SiPMs
摘要： Small animal PET scanners need to have a high spatial resolution since the size of the organs of small animals is much smaller than that of humans, and also need to have a high sensitivity since the allowed injection dose is limited by the radiation dosimetry of the small organs. To simultaneously achieve high spatial resolution and high sensitivity for a small animal PET scanner, detectors with high position resolution, high efficiency and high depth of interaction (DOI) resolution are required. In this work, three 17 × 17 pixelated LYSO arrays with crystal size of ～ 0.5 mm and an outer dimension of 10 × 10 × 20 mm3 are fabricated. The first LYSO array uses 80 μm thick BaSO4 reflector. The second and the third LYSO arrays use 65 μm thick Toray reflectors. The outermost side of the third LYSO array is also wrapped with k9 glass of the same size as the crystals in the array in order to improve the light collection and flood histogram quality for the edge crystals. The LYSO arrays are read out with two Hamamatsu SiPM arrays from both ends. The SiPM array is 4 × 4, with 3 × 3 mm2 pixel size and 0.2 mm gap in between the SiPM pixels. The SiPM array is read out with a resistor network circuit to reduce the number of signals from 16 to 4. The performance of the detector in terms of flood histograms, energy resolution, DOI resolution and timing resolution was measured. All three detectors provide good flood histograms and all crystals in an array can be clearly resolved. The average DOI resolutions of individual crystals are 1.84, 1.98 and 1.93 mm for the three detectors for events with energy E > 350 keV. The BaSO4 array has higher light output and provides a better average crystal energy resolution of 21.0 %. The photopeak amplitude of the Toray arrays changes with depth, which results in worse energy resolutions of 24.4 % and 23.8 % for the two detectors respectively. The average timing resolutions of individual crystals are 1.23, 1.27 and 1.24 ns for the three detectors for events with E > 350 keV. All three detector modules achieved high position resolution (0.5 mm crystal size), high efficiency (20 mm crystal length) and high DOI resolution (<2.0 mm) and can be used to build a high sensitivity small animal PET scanner with spatial resolution approaching the physical limit.
关键词： Dual-ended readout,Small animal PET,Depth of interaction,High resolution,SiPM
更新于2025-09-04 15:30:14
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Tau <scp>PET</scp> Imaging for Staging of Alzheimer's Disease in Down Syndrome
摘要： Alzheimer’s disease (AD) pathology and early-onset dementia develop almost universally in Down syndrome (DS). AD is defined neuropathologically by the presence of extracellular plaques of aggregated amyloid β protein and intracellular neurofibrillary tangles (NFTs) of aggregated hyperphosphorylated tau protein. The development of radiolabeled positron emission tomography (PET) ligands for amyloid plaques and tau tangles enables the longitudinal assessment of the spatial pattern of their accumulation in relation to symptomatology. Recent work indicates that amyloid pathology develops 15-20 years before neurodegeneration and symptom onset in the sporadic and autosomal dominant forms of AD, while tau pathology correlates more closely with symptomatic stages evidenced by cognitive decline and dementia. Recent work on AD biomarkers in DS illustrates similarities between DS and sporadic AD. It may soon be possible to apply recently developed staging classifications to DS to obtain a more nuanced understanding of the development AD in DS and to provide a more accurate diagnosis and prognosis in the clinic.
关键词： Tau PET,Down syndrome,Alzheimer’s disease
更新于2025-09-04 15:30:14
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[IEEE 2018 International Conference on Advances in Computing, Communications and Informatics (ICACCI) - Bangalore, India (2018.9.19-2018.9.22)] 2018 International Conference on Advances in Computing, Communications and Informatics (ICACCI) - Multi-Modal Medical Image Fusion Using Curvelet Algorithm
摘要： Medical image fusion is the process of combining images from different modalities to make the fused image more informative than any of the source images. Images of different modalities include PET, CT, SPECT and MRI. One input image will have high spatial resolution and low spectral information and another image will have high spectral resolution and vice versa. The aim of medical image fusion is to have a single image having both spatial and spectral resolution. Most commonly used transform domain methods like Curvelet transform is applied to extract more specific information from the source images. Experimental results demonstrate that fused image will have sharpened image resolution and the fusion performance is evaluated with image quality assessment metrics.
关键词： SPECT/PET,MRI,spatial and spectral resolution,Curvelet
更新于2025-09-04 15:30:14