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Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2936-2952页

作者： Liang Zhao Yizhen Pang Yangfan Zhou Jianhao Chen Hao Fu Wei Guo Weizhi Xu Xin Xue Guoqiang Su Long Sun Hua Wu Jingjing Zhang Zhanxiang Wang Qin Lin Xiaoyuan Chen Haojun Chen Department of Nuclear Medicine and Minnan PET Center Xiamen Key Laboratory of RadiopharmaceuticalsThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Radiation Oncology Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Colorectal Tumor Surgery Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Cardiothoracic Surgery Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingChina Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Neurosurgery and Department of Neuroscience Fujian Key Laboratory of Brain Tumors Diagnosis and Precision TreatmentXiamen Key Laboratory of Brain Centerthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamenChina

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor *** radionuclide therapy delivers radiation directly to tumor ***1004 is a fibroblast activation protein(FAP)-targeting radiopharmaceutical,conjugated with the albumin binder Evans Blue,which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical ***,we demonstrate that^(68)Ga/^(177)Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor *** therapy with^(177)Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor *** combination of^(177)Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice,with mice showing 100%tumor rejection upon ***,single-cell RNA sequencing(scRNA-seq),and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication,CD8^(+)T-cell activation and expansion,M1 macrophage counts,antitumor activity of neutrophils,and T-cell receptor diversity.A preliminary clinical study demonstrated that^(177)Lu-LNC1004 was well-tolerated and effective in patients with refractory ***,scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade *** was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell *** conclusion,our data supported the efficacy of immunotherapy combined with^(177)Lu-LNC1004 for cancer patients with FAP-positive tumors.

关键词： immunity retention holds

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Correlations between panoramic imagery and gamma-ray background in an urban area

arXiv

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arXiv 2021年

作者： Bandstra, Mark S. Quiter, B.J. Salathe, M. Bilton, K.J. Curtis, J.C. Goldenberg, S. Joshi, T.H.Y. The Applied Nuclear Physics Program Lawrence Berkeley National Laboratory BerkeleyCA94720 United States The Department of Nuclear Engineering University of California BerkeleyCA94720 United States The Computer Science Department The College of William and Mary WilliamsburgVA23185 United States

When searching for radiological sources in an urban area, a vehicle-borne detector system will often measure complex, varying backgrounds primarily from natural gamma-ray sources. Much work has been focused on developing spectral algorithms that retain sensitivity and minimize the false positive rate even in the presence of such spectral and temporal variability. However, information about the environment surrounding the detector system might also provide useful clues about the expected background, which if incorporated into an algorithm, could improve performance. Recent work has focused on extensive measuring and modeling of urban areas with the goal of understanding how these complex backgrounds arise. This work presents an analysis of panoramic video images and gamma-ray background data collected in Oakland, California by the Radiological Multi-sensor Analysis Platform (RadMAP) vehicle. Features were extracted from the panoramic images by semantically labeling the images and then convolving the labeled regions with the detector response. A linear model was used to relate the image-derived features to gamma-ray spectral features obtained using Non-negative Matrix Factorization (NMF) under different regularizations. We find some gamma-ray background features correlate strongly with image-derived features that measure the response-adjusted solid angle subtended by sky and buildings, and we discuss the implications for the development of future, contextually-aware detection algorithms. Copyright © 2021, The Authors. All rights reserved.

关键词： Gamma rays

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Freestanding LiPON: from Fundamental Study to Uniformly Dense Li Metal Deposition Under Zero External Pressure

arXiv

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arXiv 2022年

作者： Cheng, Diyi Wynn, Thomas Lu, Bingyu Marple, Maxwell Han, Bing Shimizu, Ryosuke Sreenarayanan, Bhagath Bickel, Jeffery Hosemann, Peter Yang, Yangyuchen Nguyen, Han Li, Weikang Zhu, Guomin Zhang, Minghao Meng, Ying Shirley Materials Science and Engineering Program University of California La Jolla San DiegoCA92121 United States Department of NanoEngineering University of California La Jolla San DiegoCA92121 United States Physical and Life Science Directorate Lawrence Livermore National Laboratory LivermoreCA94550 United States Nuclear Engineering Department University of California Berkeley BerkeleyCA94720 United States Pritzker School of Molecular Engineering University of Chicago ChicagoIL60637 United States

Lithium phosphorus oxynitride (LiPON) is a well-known amorphous thin film solid electrolyte that has been extensively studied in the last three decades. Despite the promises to pair with Li metal anode and various cathode materials, the presence of rigid substrate and LiPON's unique amorphous, air-sensitive nature set limitations to comprehensively understand its intrinsic properties for future development and applications. This work demonstrates a methodology to synthesize LiPON in a freestanding form that exhibits remarkable flexibility and a Young's modulus of ~33 GPa. Solid-state nuclear magnetic resonance (ss-NMR) and differential scanning calorimetry (DSC) results with unprecedented high signal-to-noise ratio could be obtained with such freestanding LiPON (FS-LiPON), revealing the Li/LiPON interface bonding environments quantitatively and a well-defined glass transition temperature for LiPON. Combining interfacial stress and a seeding layer, FS-LiPON demonstrates a uniform and fully dense Li metal deposition without the aid of external pressure. Such a FS-LiPON film offers new opportunities for fundamental study of LiPON material and associated interfaces, and provides perspectives for interface engineering in bulk solid-state battery. Copyright © 2022, The Authors. All rights reserved.

关键词： Solid electrolytes

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Field-Induced Criticality in YbCu4Au

arXiv

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arXiv 2024年

作者： Taniguchi, Takanori Osato, Kotaro Okabe, Hirotaka Kitazawa, Takafumi Kawamata, Masahiro Hashimoto, Shota Ikeda, Yoichi Nambu, Yusuke Sari, Dita Puspita Watanabe, Isao Nakamura, Jumpei G. Koda, Akihiro Gouchi, Jun Uwatoko, Yoshiya Kittaka, Shunichiro Sakakibara, Toshiro Mizumaki, Masaichiro Kawamura, Naomi Yamanaka, Takayoshi Hiraki, Koichi Sasaki, Takahiko Fujita, Masaki Institute for Materials Research Tohoku University Sendai980-8577 Japan Department of Physics Tohoku University Sendai980-8578 Japan Organization for Advanced Studies Tohoku University Sendai980-8577 Japan FOREST Japan Science and Technology Agency Kawaguchi Saitama332-0012 Japan Innovative Global Program College of Engineering Shibaura Institute of Technology Saitama337-8570 Japan Nuclear Structure Research Group Nishina Center for Accelerator-Based Science RIKEN Wako Saitama351-0198 Japan Institute of Materials Structure Science High-Energy Accelerator Research Organization Tsukuba305-0801 Japan The Institute for Solid State Physics The University of Tokyo Kashiwa Chiba277-8581 Japan Department of Physics Faculty of Science and Engineering Chuo University Tokyo112-8551 Japan Faculty of Science Kumamoto University 2-39-1 Kurokami Chuou-ku Kumamoto860-8555 Japan Japan Synchrotron Radiation Research Institute Sayo Hyogo679-5148 Japan Integrated Center for Science and Humanities Fukushima Medical University Fukushima960-1295 Japan

YbCu4Au is a unique material exhibiting multiple quantum fluctuations simultaneously. In this study, we investigated the field-induced criticality in YbCu4Au, based on comprehensive micro and macro measurements, including powder Xray diffraction (XRD), neutron powder diffraction (NPD), nuclear magnetic resonance, magnetization, resistivity, specific heat, muon spin rotation relaxation (μSR), and X-ray absorption spectroscopy (XAS). Single crystals of YbCu4Au were grown, and their crystal structure was determined using XRD, and NPD measurements. Magnetic successive transitions were observed below 1 T by specific heat, resistivity, NPD, and μSR measurements. XAS measurements further indicate that the valence of Yb ions (+2.93) remained unchanged above 2 T. Moreover, the change in quadrupole frequency observed in the previous study is attributable to the electric quadrupole, as the expected value of the electric quadrupole was finite under magnetic fields [S. Wada et al., Journal o f Physics: Condensed Matter, 20, 175201 (2008).]. These experimental results suggest that YbCu4Au exhibited bicritical behavior near 1 T, arising from the competition between RKKY interaction, accounting for the magnetic phases, and the Zeeman effect. © 2024, CC BY-NC-SA.

关键词： X ray absorption spectroscopy

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Monte Carlo source descriptions for unenriched uranium fuel and a PuBe neutron source

Monte Carlo source descriptions for unenriched uranium fuel ...

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2019 Transactions of the American nuclear Society, ANS 2019

作者： Ghiglieri, Cliff King, Jeffrey Nuclear Science and Engineering Program Colorado School of Mines 1500 Illinois St. GoldenCO80401 United States

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Author Correction: SARS-CoV-2 infection engenders heterogeneous ribonucleoprotein interactions to impede translation elongation in the lungs

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EXPERIMENTAL AND MOLECULAR MEDICINE 2023年第12期55卷 2609-2609页

作者： Kim, Junsoo Youn, Daehwa Choi, Seunghoon Lee, Youn Woo Sumberzul, Dulguun Yoon, Jeongeun Lee, Hanju Bae, Jong Woo Noh, Hyuna On, Dain Hong, Seung-Min An, Se-Hee Jang, Hui Jeong Kim, Seo Yeon Kim, Young Been Hwang, Ji-Yeon Lee, Hyo-Jung Kim, Hong Bin Park, Jun Won Yun, Jun-Won Shin, Jeon-Soo Seo, Jun-Young Nam, Ki Taek Choi, Kang-Seuk Lee, Ho-Young Chang, Hyeshik Seong, Je Kyung Cho, Jun Center for RNA Research Institute for Basic Science (IBS) Seoul National University Seoul Republic of Korea Interdisciplinary Program in Bioinformatics Seoul National University Seoul Republic of Korea Department of Biomedical Science and Engineering Gwangju Institute of Science and Technology (GIST) Gwangju Republic of Korea Korea Mouse Phenotyping Center (KMPC) Seoul National University Seoul Republic of Korea Laboratory of Developmental Biology and Genomics Research Institute for Veterinary Science and BK 21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Republic of Korea Department of Nuclear Medicine Seoul National University Bundang Hospital Seongnam Republic of Korea School of Biological Sciences Seoul National University Seoul Republic of Korea Laboratory of Avian Diseases Research Institute for Veterinary Science and BK 21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Republic of Korea Preclinical Research Center Seoul National University Bundang Hospital Seongnam Republic of Korea Department of Periodontology Section of Dentistry Seoul National University Bundang Hospital Seongnam Republic of Korea Department of Internal Medicine Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam Republic of Korea Division of Biomedical Convergence College of Biomedical Science Kangwon National University ChunCheon Republic of Korea Laboratory of Veterinary Toxicology College of Veterinary Medicine Seoul National University Seoul Republic of Korea Severance Biomedical Science Institute Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine Seoul Republic of Korea Department of Nuclear Medicine Seoul National University College of Medicine Seoul Republic of Korea Interdisciplinary Program and BIO MAX Institute Seoul National University

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Evaluating 3D Gamma-ray Imaging Techniques for Distributed Sources at the Fukushima Daiichi nuclear Power Station

Evaluating 3D Gamma-ray Imaging Techniques for Distributed S...

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2020 IEEE nuclear science Symposium and Medical Imaging Conference, NSS/MIC 2020

作者： Knecht, K. Hellfeld, D. Pavlovsky, R. Quiter, B. Joshi, T.H.Y. Torii, T. Furuta, Y. Vetter, K. The Nuclear Engineering Department The University of California Berkeley BerkeleyCA94720 United States The Applied Nuclear Physics Program Lawrence Berkeley National Laboratory BerkeleyCA94720 United States The Collaborative Laboratories for Advanced Decommissioning Science Japan Atomic Energy Agency 790-1 Motooka aza Ohtsuka Tomioka-machi Futaba-gun Fukushima979-1151 Japan

ISBN: (纸本)9781728176932

Portable radiation detection systems can be equipped with contextual sensors to allow free-moving 3D gamma-ray source mapping and imaging through a method called scene data fusion (SDF). The scene information provided by the contextual sensors can be used to enable 3D mapping and constrain gamma-ray image reconstruction to improve accuracy and computational efficiency. SDF can be a useful tool in a wide range of radiological and nuclear safety and security applications such as radiation mapping for contamination remediation. To demonstrate SDF for this application, Polaris-LAMP, a commercially available detector that has been integrated with contextual sensors, was hand-carried in a parking lot containing vehicles used during remediation efforts following the March 2011 Fukushima Daiichi nuclear Power Station accident. In order to detect and map potential contamination of the vehicles, proximity mapping and Compton imaging techniques have been applied to data collected over a series of short measurements, each covering different areas of the parking lot. Proximity mapping successfully identified which vehicles are contaminated, but Compton imaging further improved localization of intensity to key vehicle features on top of distributed contamination, demonstrating the utility of SDF in radiation mapping of unknown distributed source environments. Methods to stitch multiple reconstructions together were also developed, allowing the creation of large area radiation maps that are globally consistent. The work presented here illustrates the utility of SDF with an contextual-sensor enhanced commercial radiation detection and imaging system deployed in a hand-portable format to effectively map extended areas and localize radiological contamination within minutes which is impossible to achieve with conventional means with hand-portable radiation detectors or statically deployed gamma-ray imagers. © 2020 IEEE

关键词： Contamination

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Pale Red Dot: A Large, Robust Architecture for Human Settlements on Mars

Pale Red Dot: A Large, Robust Architecture for Human Settlem...

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Accelerating Space Commerce, Exploration, and New Discovery Conference, ASCEND 2023

作者： Lordos, George Hoying, Madelyn McKinney, Lanie Webb, Alisa Lin, Yuying Martin, Estelle Beilstein, John Miller, Duncan Villegas, David Sepulveda, Francisco AlSadah, Yousif Iyer, Divya O’Neill, Cormac Patel, Palak Garcia, Ignacio Arzuaga Azzouz, H. Chan, Wing Lam Eyre, Ezra Gleason, Dane Romero, Elizabeth Arias, Liliana Orozco, Omar Gentgen, Chloe Latyshev, Kir Hoffman, Jeffrey de Weck, Olivier Ikinci, Meltem Lordos, Alexandros Aeronautics and Astronautics Massachusetts Institute of Technology 33-409 CambridgeMA02139 United States Massachusetts Institute of Technology Harvard-MIT Health Sciences and Technology Program and MIT Aeronautics and Astronautics 33-409 CambridgeMA02139 United States Massachusetts Institute of Technology CambridgeMA02139 United States Aeronautics and Astronautics Massachusetts Institute of Technology 77 Mass Ave. 33-409 CambridgeMA02139 United States System Design and Management Massachusetts Institute of Technology 77 Mass Ave. E40-300 CambridgeMA02139 United States Mechanical Engineering Massachusetts Institute of Technology 77 Mass Ave. 33-409 CambridgeMA02139 United States Civil and Environmental Engineering Massachusetts Institute of Technology 77 Mass Ave. CambridgeMA02139 United States Electrical Engineering Massachusetts Institute of Technology 77 Mass Ave. CambridgeMA02139 United States Nuclear Science and Engineering Massachusetts Institute of Technology 77 Mass Ave. CambridgeMA02139 United States Computer Science and Engineering Massachusetts Institute of Technology 77 Mass Ave. CambridgeMA02139 United States Massachusetts Institute of Technology 77 Mass Ave. 37-219 CambridgeMA02139 United States Massachusetts Institute of Technology 77 Mass Ave. 33-410 CambridgeMA02139 United States Behavioral Economics University of Cyprus Nicosia Cyprus Department of Psychology University of Cyprus Nicosia Cyprus

ISBN: (数字)9781624107054

ISBN: (纸本)9781624107054

We propose a ten-yearMars mission to establish Earth-independence and support efficient, safe, and sustainable science and exploration goals. The campaign begins with a series of precursor missions, starting with the Artemis program, followed by robotic missions to performsite surveys and selection, de-risk technologies, and to start stockpiling in-situ water and propellant. Robotic Cargo Starships would depart first in 2035 to deliver and deploy approximately 5,800 tons of habitats, nuclear microreactors, farmmodules, manufacturing and ISRU systems. In 2040, two Crew Starships carrying 36 persons would land onMars to establish two close-proximity villages. The lifecycle cost is estimated at $81 billion, with a peak annual cost of $6.6 billion. To meet RASC-AL competition requirements, intended to motivate the exploration of highly self-reliant architecture concepts, resupply from Earth was constrained to only 5 metric tons every two years and minimum surface endurance was set at 7 years. The risks to human life and to critical systems increase exponentially over a minimally-resupplied, 7-10 year mission toMars. Our approach focused on identifying capabilities to mitigate known and unknown risks. Using a high-fidelity crew time model, we found that large architectures, with their economies of scale and productivity gains from specialization, are essential to robustly support the necessary capabilities. The model also shows that small 7-year missions of 12 persons or less cannot provide value in terms of free surface traverse time for science and exploration. Given the necessity of a large, complex architecture, we then sought out efficiencies and synergies (value engineering) in order to make the mission feasible and affordable. In the process, we identified more benefits that are enabled only by large missions, including the creation of a true community on Mars with sufficient social complexity for humans to thrive, and the geopolitically compelling option to inclu

关键词： Value engineering

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Multimodal Spatial Attention Network for Automatic Head and Neck Tumor Segmentation in FDG-PET and CT Images 1

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2nd 3D Head and Neck Tumor Segmentation in PET/CT Challenge, HECKTOR 2021, held in conjunction with 24th International Conference on Medical Image Computing and Computer-Assisted Intervention, MICCAI 2021

作者： Cho, Minjeong Choi, Yujin Hwang, Donghwi Yie, Si Young Kim, Hanvit Lee, Jae Sung School of Electrical and Electronics Engineering Chung-Ang University Seoul06974 Korea Republic of Department of Biomedical Engineering Kyunghee University College of Electronics and Information 1732 Deogyeong-daero Giheung-gu Gyeonggi-do Yongin-si Korea Republic of Department of Nuclear Medicine Seoul National University College of Medicine Seoul03080 Korea Republic of Department of Biomedical Sciences Seoul National University College of Medicine Seoul03080 Korea Republic of Interdisciplinary Program in Bioengineering Seoul National University Graduate School Seoul Korea Republic of Integrated Major in Innovative Medical Science Seoul National University Graduate School Seoul Korea Republic of Ulsan Korea Republic of Artificial Intelligence Institute Seoul National University Seoul08826 Korea Republic of Brightonix Imaging Inc. Seoul04782 Korea Republic of

ISBN: (数字)9783030982539

ISBN: (纸本)9783030982522

Quantitative positron emission tomography/computed tomography (PET/CT), owing to the functional metabolic information and anatomical information of the human body that it presents, is useful to achieve accurate tumor delineation. However, manual annotation of a Volume Of Interest (VOI) is a labor-intensive and time-consuming task. In this study, we automatically segmented the Head and Neck (H&N) primary tumor in combined PET/CT images. Herein, we propose a convolutional neural network named Multimodal Spatial Attention Network (MSA-Net), supplemented with a Spatial Attention Module (SAM), which uses a PET image as an input. We evaluated this model on the MICCAI 2021 HEad and neCK TumOR (HECKTOR) segmentation challenge dataset. Our method delivered a competitive cross-validation efficiency, with Dice Similarity Coefficient (DSC) 0.757, precision 0.788, and recall 0.785. When we tested out method on test dataset, we achieved an average DSC and Hausdorff Distance at 95% (HD95) of 0.766 and 3.155 respectively. Our team name is ‘Heck_Uihak’. © 2022, Springer Nature Switzerland AG.

关键词： Tumors

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An Approach for 3D Microprinting Soft Robotic Surgical Tools at 1.5 French Length Scales for Endovascular Interventions

An Approach for 3D Microprinting Soft Robotic Surgical Tools...

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IEEE International Conference on Soft Robotics (RoboSoft)

作者： Bailey M. Felix Olivia M. Young Jordi T. Andreou Nicholas Portwood Kieran J. Barvenik Noah Barnes Clifford R. Weiss Christopher R. Bailey Dheeraj Gandhi Miroslaw Janowski Jeremy D. Brown Eleonora Tubaldi Mark Fuge Axel Krieger Ryan D. Sochol Department of Bioengineering University of Maryland College Park MD USA Department of Mechanical Engineering University of Maryland College Park MD USA Department of Mechanical Engineering Johns Hopkins University Baltimore MD USA The Russell H. Morgan Department of Radiology and Radiological Science Division of Vascular and Interventional Radiology Johns Hopkins University School of Medicine Baltimore MD USA Department of Diagnostic Radiology and Nuclear Medicine Program in Image Guided Neurointerventions University of Maryland School of Medicine Baltimore MD USA Maryland Robotics Center University of Maryland College Park MD USA Robert E. Fischell Institute for Biomedical Devices University of Maryland College Park MD USA

A wide range of endovascular interventions rely on surgical tools such as guidewire-catheter systems for navigating through blood vessels to, for example, deliver embolic materials, stents, and/or therapeutic agents to target sites as well as biopsy tools (e.g., forceps and punch needles) for medical diagnostics. In response to the difficulties in maneuvering such endovascular instruments safely and effectively to access intended sites in the body, researchers have developed an array of soft robotic surgical tools that harness fluidic (e.g., pneumatic or hydraulic) actuation schemes to support on-demand steering and control. Despite considerable progress, scaling these tools down to the sizes required for medical procedures such as cerebral aneurysm treatment and liver chemoembolization have been hindered by manufacturing-induced constraints. To provide a pathway to overcome these miniaturization challenges, this work presents a novel additive manufacturing strategy for 3D microprinting integrated soft actuators directly atop multilumen microfluidic tubing via “Two-Photon Direct Laser Writing (DLW)”. As an exemplar, a two-actuator tip was 3D printed onto custom dual-lumen tubing-resulting in a system akin to a 1.5 French (Fr) guidewire with a steerable tip. Experimental results revealed independent actuator control via the discretized lumens, with tip bending of approximately 60° under input pressures of 130 kPa via hydraulic actuation. These results suggest that the presented strategy could be extended to achieve new classes of fluidically actuated soft robotic surgical tools at unprecedented length scales for emerging applications in minimally invasive surgery.

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