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- 摘要
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- 实验方案
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Multimodal imaging of the receptor for advanced glycation end-products with molecularly targeted nanoparticles
摘要： The receptor for advanced glycation end-products (RAGE) is central to multiple disease states, including diabetes-related conditions such as peripheral arterial disease (PAD). Despite RAGE’s importance in these pathologies, there remains a need for a molecular imaging agent that can accurately assess RAGE levels in vivo. Therefore, we have developed a multimodal nanoparticle-based imaging agent targeted at RAGE with the well-characterized RAGE ligand, carboxymethyllysine (CML)-modified human serum albumin (HSA). Methods: A multimodal tracer (64Cu-Rho-G4-CML) was developed using a generation-4 (G4) polyamidoamine (PAMAM) dendrimer, conjugated with both rhodamine and copper-64 (64Cu) chelator (NOTA) for optical and PET imaging, respectively. First, 64Cu-Rho-G4-CML and its non-targeted analogue (64Cu-Rho-G4-HSA) were evaluated chemically using techniques such as dynamic light scattering (DLS), electron microscopy and nuclear magnetic resonance (NMR). The tracers’ binding capabilities were examined at the cellular level and optimized using live and fixed HUVEC cells grown in 5.5-30 mM glucose, followed by in vivo PET-CT imaging, where the probes’ kinetics, biodistribution, and RAGE targeting properties were examined in a murine model of hindlimb ischemia. Finally, histological assessment of RAGE levels in both ischemic and non-ischemic tissues was performed. Conclusions: Our RAGE-targeted probe demonstrated an average size of 450 nm, a Kd of 340-390 nM, rapid blood clearance, and a 3.4 times greater PET uptake in ischemic RAGE-expressing hindlimbs than their non-ischemic counterpart. We successfully demonstrated increased RAGE expression in a murine model of hindlimb ischemia and the feasibility for non-invasive examination of cellular, tissue, and whole-body RAGE levels with a molecularly targeted tracer.
关键词： multimodal imaging,inflammation,receptor for advanced glycation end-products,hindlimb ischemia,PET-CT
更新于2025-09-23 15:21:01
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Fast and efficient detection of 511 keV photons using Cherenkov light in PbF <sub/>2</sub> crystal, coupled to a MCP-PMT and SAMPIC digitization module
摘要： We study the possibility to use the Cherenkov light for the e?cient detection of 511 keV photons with the goal to use it in TOF-PET. We designed and tested two detection modules consisting of PbF2 crystals attached to Planacon MCP-PMT XP85012. Ampli?ed PMT signals are digitized by the SAMPIC module with high readout rate, up to 105 events/s, and a negligible contribution to the time resolution, below 20 ps (FWHM). We developed a fast 2D scanning system to calibrate the PMT time response and studied in details the timing characteristics of the Planacon PMT. Using a radioactive 22Na source we measured a detection e?ciency of 24% for 511 keV photons in a 10 mm thick crystal and a coincidence resolving time of 280 ps. We analyzed the main factors limiting the time resolution of the large-surface detection module and proposed solutions to improve it, which will be tested in our future project.
关键词： Photon detectors for UV, visible and IR photons (vacuum) (photomultipliers, HPDs, others),Cherenkov and transition radiation,Gamma camera, SPECT, PET PET/CT, coronary CT angiography (CTA)
更新于2025-09-23 15:19:57
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The influence of minimal misalignment on the repeatability of PET images examined by the repositioning of point sources
摘要： Objective: We aimed to evaluate the influence of the minimal misalignment of the hot spot on the repeatability of PET images using the repositioning of point sources. Methods: Point sources with an inner-diameter of 1 mm were made with 1μL of 18F solution. Seven point sources were placed on the x-axis in the field-of-view. For fixed position imaging, PET data were acquired for 10 min 5 times serially. For variable position imaging, PET data were acquired for 10 minutes each with the point sources placed at 0 mm, ±0.5 mm, and ±1.0 mm in the x-axis direction. The data were reconstructed using ordered-subsets expectation maximization (OSEM) and OSEM with point-spread function (OSEM+PSF) algorithms. The image matrix was 128×128, 200×200, 256×256, 400×400, and 512×512 pixels. The normalized maximum count (rMax), the variation of rMax (CVmax) and full width at half maximum (FWHM) were analyzed. Results: The hot spots on OSEM images far from the center became faint and broad, while those on the OSEM+PSF images became small and dense. Although the rMax was overestimated at the 5 cm position on OSEM image, those at other positions were overestimated on OSEM+PSF images with a matrix size of ≥256×256. The rMax showed a similar pattern in fixed and variable position images. The CVmax in fixed position OSEM images were <2%, irrespective of the matrix size. In contrast, the CVmax in variable position images were higher in comparison to fixed position images. The CVmax of the OSEM+PSF images were higher in comparison to OSEM images. The FWHM increased at positions far from the center on OSEM image, while that was stable at all positions on OSEM+PSF images. Conclusion: The repeatability of the small hot spot was affected by the minimal misalignment, especially on the OSEM+PSF images. Precise positioning is necessary if PET is to be used as a biomarker. Professions should recognize that the PSF correction deteriorates the repeatability of the small hot spot although it improves the spatial resolution of PET images.
关键词： repositioning,repeatability,point-spread function,PET/CT
更新于2025-09-19 17:15:36
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Diagnostic performance of fluorine-18 fluorodeoxyglucose positron emission tomography in the management of solitary pulmonary nodule: a meta-analysis
摘要： Background: In the setting of solitary pulmonary nodules (SPNs), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is considered a useful non-invasive diagnostic tool though false positive (FP) and false negative (FN) results affects accuracy due to different conditions, such as inflammatory diseases or low-uptake neoplasms. Aim of this study is to evaluate overall diagnostic performance of 18F-FDG-PET/CT for malignant pulmonary nodules. Methods: A computerized research, including published articles from 2012 and 2017, was carried out. 18F-FDG-PET/CT overall sensitivity (Se), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), diagnostic index and odds ratio were pooled. No selection-bias were found according to asymmetry test. Results: A total of twelve studies were included in the meta-analysis. The pooled Se, Spe, PLR, NLR, PPV, NPV and accuracy index (AI) with relative 95% confidence intervals (CI) were 0.819 (95% CI: 0.794–0.843), 0.624 (95% CI: 0.582–0.665), 2.190 (95% CI: 1.950–2.440), 0.290 (95% CI: 0.250–0.330), 0.802 (95% CI: 0.783–0.819), 0.652 (95% CI: 0.618–0.684) and 0.649 (95% CI: 0.625–0.673), respectively. The diagnostic odds ratio (DOR) was 7.049 with a relative 95% CI between 5.550 and 8.944. Conclusions: The results suggest 18F-FDG-PET/CT has good diagnostic accuracy in SPNs evaluation; but, it should not be considered as a discriminatory test rather than a method to be included in a clinical and diagnostic pathway.
关键词： Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT),solitary pulmonary nodules (SPNs),lung cancer
更新于2025-09-19 17:15:36
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[IEEE 2019 IEEE 46th Photovoltaic Specialists Conference (PVSC) - Chicago, IL, USA (2019.6.16-2019.6.21)] 2019 IEEE 46th Photovoltaic Specialists Conference (PVSC) - Spatially Resolved Material Quality Prediction Via Constrained Deep Learning
摘要： Positron emission tomography (PET) images are typically reconstructed with an in-plane pixel size of approximately 4 mm for cancer imaging. The objective of this work was to evaluate the effect of using smaller pixels on general oncologic lesion-detection. A series of observer studies was performed using experimental phantom data from the Utah PET Lesion Detection Database, which modeled whole-body FDG PET cancer imaging of a 92 kg patient. The data comprised 24 scans over 4 days on a Biograph mCT time-of-flight (TOF) PET/CT scanner, with up to 23 lesions (diam. 6–16 mm) distributed throughout the phantom each day. Images were reconstructed with 2.036 mm and 4.073 mm pixels using ordered-subsets expectation-maximization (OSEM) both with and without point spread function (PSF) modeling and TOF. Detection performance was assessed using the channelized non-prewhitened numerical observer with localization receiver operating characteristic (LROC) analysis. Tumor localization performance and the area under the LROC curve were then analyzed as functions of the pixel size. In all cases, the images with ～2 mm pixels provided higher detection performance than those with ～4 mm pixels. The degree of improvement from the smaller pixels was larger than that offered by PSF modeling for these data, and provided roughly half the benefit of using TOF. Key results were confirmed by two human observers, who read subsets of the test data. This study suggests that a significant improvement in tumor detection performance for PET can be attained by using smaller voxel sizes than commonly used at many centers. The primary drawback is a 4-fold increase in reconstruction time and data storage requirements.
关键词： PET/CT reconstruction,PET/CT,image reconstruction,Image quality assessment
更新于2025-09-19 17:13:59
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[IEEE 2019 IEEE 46th Photovoltaic Specialists Conference (PVSC) - Chicago, IL, USA (2019.6.16-2019.6.21)] 2019 IEEE 46th Photovoltaic Specialists Conference (PVSC) - Photovoltaic Inverter Momentary Cessation: Recovery Process is Key
摘要： Positron emission tomography (PET) images are typically reconstructed with an in-plane pixel size of approximately 4 mm for cancer imaging. The objective of this work was to evaluate the effect of using smaller pixels on general oncologic lesion-detection. A series of observer studies was performed using experimental phantom data from the Utah PET Lesion Detection Database, which modeled whole-body FDG PET cancer imaging of a 92 kg patient. The data comprised 24 scans over 4 days on a Biograph mCT time-of-flight (TOF) PET/CT scanner, with up to 23 lesions (diam. 6–16 mm) distributed throughout the phantom each day. Images were reconstructed with 2.036 mm and 4.073 mm pixels using ordered-subsets expectation-maximization (OSEM) both with and without point spread function (PSF) modeling and TOF. Detection performance was assessed using the channelized non-prewhitened numerical observer with localization receiver operating characteristic (LROC) analysis. Tumor localization performance and the area under the LROC curve were then analyzed as functions of the pixel size. In all cases, the images with ～2 mm pixels provided higher detection performance than those with ～4 mm pixels. The degree of improvement from the smaller pixels was larger than that offered by PSF modeling for these data, and provided roughly half the benefit of using TOF. Key results were confirmed by two human observers, who read subsets of the test data. This study suggests that a significant improvement in tumor detection performance for PET can be attained by using smaller voxel sizes than commonly used at many centers. The primary drawback is a 4-fold increase in reconstruction time and data storage requirements.
关键词： Image quality assessment,PET/CT reconstruction,PET/CT,image reconstruction
更新于2025-09-19 17:13:59
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PET/CT imaging with a <sup>18</sup> F-labeled galactodendritic unit in a galectin-1 overexpressing orthotopic bladder cancer model
摘要： Galectins are carbohydrate-binding proteins overexpressed in bladder cancer (BCa) cells. Dendritic galactose moieties have a high affinity for galectin-expressing tumor cells. We radiolabeled a dendritic galactose carbohydrate with fluorine-18 – 18F-labeled galactodendritic unit 4 – and examined its potential in imaging urothelial malignancies. Methods: The 18F-labeled 1st generation galactodendritic unit 4 was obtained from its tosylate precursor. We conducted in vivo studies in galectin-expressing UMUC3 orthotopic BCa model to determine the ability of 18F-labeled galactodendritic unit 4 to image BCa. Results: Intravesical administration of 18F-labeled galactodendritic unit 4 allowed specific accumulation of the carbohydrate radiotracer in galectin-1 overexpressing UMUC3 orthotopic tumors when imaged with PET. The 18F-labeled galactodendritic unit 4 was not found to accumulate in non-tumor murine bladders. Conclusion: The 18F-labeled galactodendritic unit 4 and similar analogs may be clinically relevant and exploitable for PET imaging of galectin-1 overexpressing bladder tumors.
关键词： PET/CT imaging,bladder cancer,18F-radiochemistry,galectins,dendritic carbohydrate
更新于2025-09-19 17:13:59
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[IEEE 2019 16th International Conference on the European Energy Market (EEM) - Ljubljana, Slovenia (2019.9.18-2019.9.20)] 2019 16th International Conference on the European Energy Market (EEM) - Shapley-Value-Based Distribution of the Costs of Solar Photovoltaic Plant Grid Connection
摘要： Positron emission tomography (PET) images are typically reconstructed with an in-plane pixel size of approximately 4 mm for cancer imaging. The objective of this work was to evaluate the effect of using smaller pixels on general oncologic lesion-detection. A series of observer studies was performed using experimental phantom data from the Utah PET Lesion Detection Database, which modeled whole-body FDG PET cancer imaging of a 92 kg patient. The data comprised 24 scans over 4 days on a Biograph mCT time-of-flight (TOF) PET/CT scanner, with up to 23 lesions (diam. 6–16 mm) distributed throughout the phantom each day. Images were reconstructed with 2.036 mm and 4.073 mm pixels using ordered-subsets expectation-maximization (OSEM) both with and without point spread function (PSF) modeling and TOF. Detection performance was assessed using the channelized non-prewhitened numerical observer with localization receiver operating characteristic (LROC) analysis. Tumor localization performance and the area under the LROC curve were then analyzed as functions of the pixel size. In all cases, the images with ～2 mm pixels provided higher detection performance than those with ～4 mm pixels. The degree of improvement from the smaller pixels was larger than that offered by PSF modeling for these data, and provided roughly half the benefit of using TOF. Key results were confirmed by two human observers, who read subsets of the test data. This study suggests that a significant improvement in tumor detection performance for PET can be attained by using smaller voxel sizes than commonly used at many centers. The primary drawback is a 4-fold increase in reconstruction time and data storage requirements.
关键词： PET/CT reconstruction,PET/CT,image reconstruction,Image quality assessment
更新于2025-09-16 10:30:52
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Surveillance With PET/CT and Liquid Biopsies of Stage I-III Lung Cancer Patients After Completion of Definitive Therapy: A Randomized Controlled Trial (SUPER)
摘要： Despite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intent have a high risk of relapse, leading to a dismal prognosis. More knowledge on the ef?cacy of surveillance with both current and new technologies as well as on the impact on patient treatment, quality of life, and survival are urgently needed. We therefore designed a randomized phase 3 trial. In one arm, every other computed tomography (CT) scan is replaced by positron emission tomography/CT, the other arm is the standard follow-up scheme with CT. The standard arm is identical to the current national Danish follow-up program. The primary endpoint is to compare the number of relapses treatable with curative intent in the 2 arms. We aim to include 750 patients over a 3-year period. Additionally, we will test the feasibility of noninvasive lung cancer diagnostics and surveillance in the form of circulating tumor DNA analysis. For this purpose, blood samples are collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions.
关键词： Liquid biopsies,NSCLC,Surveillance,QoL,PET/CT
更新于2025-09-12 10:27:22
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Evaluation of 64Cu radiolabeled anti-hPD-L1 Nb6 for positron emission tomography imaging in lung cancer tumor mice model
摘要： Recently, we selected a novel anti-hPD-L1-specific HCAb named Nb6 with high affinity (EC50= 0.65 ng/mL) for potential hPD-L1 targeted non-invasive PET imaging. In this research, Nb6 was conjugated with the bifunctional chelator NCS-Bz-NOTA ((2-[(4-Isothiocyanophenyl) methyl]-1,4,7-triazacy-clononane-1,4,7-triacetic acid)) and further labeled with radio-nuclide 64Cu. 64Cu-NOTA-Nb6 was prepared with over 95% labeling yield, over 99% radiochemical purity and 14~16 GBq/μmol specific activity after PD-10 column purification. It shows good stability in 0.01 M PBS and 5% HSA solutions. 64Cu-NOTA-Nb6 has a high binding affinity to 3.60 nM which was tested by human lung adenocarcinoma A549 cell lines. Tumor lesion can be clearly observed from 20 h to 38 h by Micro-PET equipment after 64Cu-NOTA-Nb6 administration. The study revealed that 64Cu-NOTA-Nb6 has good lesion detection ability, high ratios between tumor and non-tumor signal and can specifically target A549 xenografted tumor model. Taken together of good stability, high binding affinity, and tumor detection ability, 64Cu labeled Nb6 is a promising radio-tracer in diagnosing of hPD-L1 overexpression tumor, supposed to monitor PD-L1overexpression tumor progression and guide targeted therapy with PET molecular imaging.
关键词： Lung cancer,PET/CT imaging,64Cu-NOTA-Nb6,heavy chain-only antibody (HCAb),PD-L1
更新于2025-09-12 10:27:22