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Enhancing Anti-PD-1/PD-L1 Immune Checkpoint Inhibitory Cancer Therapy by CD276-Targeted Photodynamic Ablation of Tumor Cells and Tumor Vasculature
摘要： Antiangiogenic therapies have been demonstrated to improve the efficacy of immune checkpoint inhibition by overcoming the immunosuppressive status of tumor microenvironment. However, most of the current antiangiogenic agents cannot discriminate tumor angiogenesis from physiological angiogenesis. The aim of this study was to investigate whether a photodynamic therapy (PDT) agent that targets CD276, a receptor overexpressed in various tumor cells and tumor vasculature but with limited expression in normal tissue vasculature, could improve the tumor inhibitory efficacy of PD-1/PD-L1 blockade. A CD276-targeting agent (IRD-αCD276/Fab) was synthesized by conjugating the Fab fragment of an anti-CD276 antibody with a photosensitizer IRDye700. The in vivo tumor-targeting and therapeutic effect of IRD-αCD276/Fab with or without anti-PD-1/PD-L1 blockade was tested in subcutaneous and lung metastatic tumor models. PDT using IRD-αCD276/Fab significantly suppressed the growth of subcutaneous 4T1 tumor and inhibited its lung metastasis. Moreover, it triggered in vivo antitumor immunity by increasing the activation and maturation of dendritic cells. Tumor PD-L1 levels were also markedly increased after PDT using IRD-αCD276/Fab, as evidenced by noninvasive PD-L1-targeted small-animal PET imaging. In combination with anti-PD-1/PD-L1 blockade, IRD-αCD276/Fab PDT markedly suppressed the growth of tumors and prevented their metastasis to the lung by recruiting the tumor infiltration of CD8+ T cells. Our data provide evidence for the role of CD276-targeted PDT for local immune modulation, and its combination with PD-L1/PD-1 axis inhibition is a promising strategy for eliminating primary tumors as well as disseminated metastases, by generating local and systemic antitumor responses.
关键词： Molecular imaging,Checkpoint inhibition,Photoimmunotherapy,PET imaging,Angiogenesis
更新于2025-09-23 15:21:01
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Optimized feature extraction for radiomics analysis of <sup>18</sup> F-FDG-PET imaging
摘要： Radiomics analysis of 18F-FDG-PET/CT images promises for an improved in-vivo disease characterization. To date, several studies reported significant variations in textural features due to differences in patient preparation, imaging protocols, lesion delineation and feature extraction. Our objective was to study variations of features prior to a radiomics analysis of 18F-FDG-PET data and to identify those feature extraction and imaging protocol parameters that minimize radiomic feature variations across PET imaging systems. Methods. A whole-body National Electrical Manufacturers Association image quality phantom was imaged with 13 PET/CT systems at 12 different sites following local protocols. We selected 37 radiomic features related to the four largest spheres (17-37 mm) in the phantom. Based on a combined analysis of voxel size, bin size and lesion volume changes, feature and imaging system ranks were established. A 1-way analysis of variance (ANOVA) was performed over voxel size, bin size and lesion volume subgroups to identify the dependency and the trend change of feature variations across these parameters. Results. Feature ranking revealed that the gray-level co-occurrence matrix (GLCM) and shape features are the least sensitive to PET imaging system variations. Imaging system ranking illustrated that the use of point-spread function (PSF), small voxel sizes and narrow Gaussian post-filtering helped minimize feature variations. ANOVA subgroup analysis indicated that variations of each of the 37 features and for a given voxel size and bin size parameter can be minimized. Conclusions. Our study provides guidance to selecting optimized features from 18F-FDG-PET/CT studies. We were able to demonstrate that feature variations can be minimized for selected image parameters and imaging systems. These results can help imaging specialists and feature engineers in increasing the quality of future radiomic studies involving PET/CT.
关键词： radiomics,18F-FDG PET/CT,feature extraction
更新于2025-09-23 15:21:01
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AN INTERNATIONAL SURVEY ON CLINICAL REPORTING OF DUAL-MODALITY PET/CT IMAGING EXAMINATIONS: A STARTING POINT FOR CROSS-SPECIALTY ENGAGEMENT
摘要： Introduction. Combined PET/CT imaging has become an integral part of patient management, particularly in oncology. Following the imaging examination, a report of the findings is created by the expert readers and sent to the referrers as a basis for subsequent management decision-making for their patients. In view of the known wide variation in operational models of PET/CT imaging, we initiated a survey of PET/CT users regarding their approaches towards PET/CT reporting. Materials and Methods. An electronic survey was composed with a set of 28 questions regarding the demographics and professional background of the survey responders, as well as questions regarding the structure and quality of PET/CT reports, including the type of reported information, the use of reporting standards and the mix of reporting and presenting experts. The survey was active during six weeks in early 2018. A total of 242 responses were collected worldwide. Results. The responders were mainly from Europe (78%), Of all responders, 21% were nuclear medicine specialists, 41% were radiologists, 22% were dual-board certified, 9% were residents in either nuclear medicine or radiology, and 5% were medical physicists, radiographers or oncologists. A slim majority (55%) of responses indicated reports being done according to the EANM/SNMMI 2015 guidelines for 18F-FDG-PET/CT imaging but 30% responders were unaware of these guidelines. Report structures varied across sites with most sites (38%) reporting the PET with supplementary localization information from CT, while 27% sites report along the lines of a CT report with supplementary PET information. One third of the reports include information on the TNM stage of the oncology patient in all reports, while 34% and 12% reports include this information occasionally or only for selected tumors, respectively. In case of therapy response assessment, various well-established criteria are employed ranging from 15% (EORTC) to 57% (Deauville) of cases. Conclusions. Broad variation in the PET/CT reporting strategies adopted for oncology studies and widespread lack of awareness of existing guidelines for PET/CT reporting are evident from responses to this survey, raising concerns as to whether reporting clinicians are optimally utilizing the complementary information from each modality. Greater efforts are needed to ensure harmonization of reporting practices.
关键词： clinical routine,PET/CT imaging,reporting
更新于2025-09-23 15:21:01
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3D auto-context-based locality adaptive multi-modality GANs for PET synthesis
摘要： Positron emission tomography (PET) has been substantially used recently. To minimize the potential health risk caused by the tracer radiation inherent to PET scans, it is of great interest to synthesize the high-quality PET image from the low-dose one to reduce the radiation exposure. In this paper, we propose a 3D auto-context-based locality adaptive multi-modality generative adversarial networks model (LA-GANs) to synthesize the high-quality FDG PET image from the low-dose one with the accompanying MRI images that provide anatomical information. Our work has four contributions. First, different from the traditional methods that treat each image modality as an input channel and apply the same kernel to convolve the whole image, we argue that the contributions of different modalities could vary at different image locations, and therefore a unified kernel for a whole image is not optimal. To address this issue, we propose a locality adaptive strategy for multi-modality fusion. Second, we utilize 1×1×1 kernel to learn this locality adaptive fusion so that the number of additional parameters incurred by our method is kept minimum. Third, the proposed locality adaptive fusion mechanism is learned jointly with the PET image synthesis in a 3D conditional GANs model, which generates high-quality PET images by employing large-sized image patches and hierarchical features. Fourth, we apply the auto-context strategy to our scheme and propose an auto-context LA-GANs model to further refine the quality of synthesized images. Experimental results show that our method outperforms the traditional multi-modality fusion methods used in deep networks, as well as the state-of-the-art PET estimation approaches.
关键词： Image synthesis,Positron emission topography (PET),Locality adaptive fusion,Generative adversarial networks (GANs),Multi-modality
更新于2025-09-23 15:21:01
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Quantitative assessment of metabolic tumor burden in molecular subtypes of primary breast cancer with FDG PET/CT
摘要： We aimed to quantitatively evaluate volumetric metabolic tumor burden including metabolic tumor volume and total lesion glycolysis in different molecular subtypes of breast cancer using 18F-fluorodeoxyglucose (FDG) positron emission tomography/ computed tomography (PET/CT). This study involved 99 female patients with pathologic diagnosis of primary breast cancer, who underwent 18F-FDG PET/CT before any therapy. Patients were divided into subtypes of luminal A, luminal B, ERBB2+, and basal-like based on the immunohistochemistry results. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) before and after correction for lean body mass were achieved and compared. Correlations between metabolic tumor burden and Ki-67 were analyzed and diagnostic performances of volumetric metabolic parameters were evaluated. TLG values were significantly different between each molecular subtype, while MTV values were not. Values of TLG were significantly reduced after normalizing for lean body mass in each subtype. Both of them showed correlations with Ki-67 and presented high diagnostic ability in identifying patients with basal-like breast cancer from the rest. TLGs before and after normalizing for the lean body mass had similar diagnostic performances in differentiating patients of basal-like subtype from the rest. Metabolic tumor burden could comprehensively reflect tumor metabolic differences of molecular subtypes of breast cancer, and it can serve to help differentiate patients with basal-like breast cancer.
关键词： metabolic tumor burden,FDG PET/CT,breast cancer,volumetric parameters,molecular subtypes
更新于2025-09-23 15:21:01
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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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Handbook of Neuro-Oncology Neuroimaging || Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT) Physics
摘要： The purpose of emission tomography is to estimate the distribution of a radiotracer from external measurements of the pattern of photons emerging from the brain. Some of these photons are detected, and certain information about them recorded, by the scanner. These external measurements are termed “projections,” and each measurement in a projection represents, ideally, the sum of radioactivity concentration along a line through the brain. From these measured projection data sets and knowledge of certain aspects of the single-photon emission computed tomography (SPECT) or positron emission tomography (PET) instrument, estimated images of the distribution of radioactivity are mathematically reconstructed. All modern SPECT and PET scanners image the three-dimensional (3D) distribution of radioactivity, either as a stack of two-dimensional (2D) transaxial images or directly as a 3D volume.
关键词： Single-Photon Emission Computed Tomography,Positron Emission Tomography,Image Reconstruction,Radiotracer,SPECT,PET,Radioactivity Distribution,Physics
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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Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): a multicentre, open-label, randomised, controlled trial
摘要： With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer.
关键词： chemoradiotherapy,Imaging-based target volume reduction,randomised,multicentre,controlled trial,open-label,PET-Plan,locally advanced non-small-cell lung cancer
更新于2025-09-23 15:19:57
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Photo-controlled RAFT polymerization mediated by organic/inorganic hybrid photoredox catalysts: enhanced catalytic efficiency
摘要： Photo-controlled RAFT polymerization mediated by organic/inorganic hybrid photoredox catalysts: enhanced catalytic efficiency. Metalloporphyrins (MTPPs) play an important role in the conversion of light energy to initiate photo-induced electron transfer–reversible addition–fragmentation chain transfer (PET-RAFT) polymerization, in which zinc tetraphenylporphyrin (ZnTPP) has attracted a high degree of attention. However, the self-aggregation effect of porphyrins in some organic solvents such as dimethyl sulphoxide (DMSO) leads to quenching of the excited state of the MTPPs and reduces their photocatalytic capacity in a concentration-dependent manner. In this study, a ZnTPP–POSS organic/inorganic complex was fabricated by linking a polyhedral oligomeric silsesquioxane (POSS) to ZnTPP. The aggregation of the photocatalyst was efficiently depressed in a PET-RAFT polymerization which was catalyzed by ZnTPP–POSS under green light (λmax = 515 nm, 3 mW cm?2). Compared to ZnTPP, the reactions using ZnTPP–POSS as the photocatalyst were well controlled for different monomers with accelerated reaction rates. Well-defined block copolymers were successfully achieved by the chain-extension reaction which demonstrates the high-end fidelities of this polymerization approach.
关键词： Photo-controlled RAFT polymerization,PET-RAFT polymerization,organic/inorganic hybrid photoredox catalysts,block copolymers,ZnTPP–POSS
更新于2025-09-23 15:19:57