Directional sensor for radioluminescence microscopy of next-generation tumor models

用于下一代肿瘤模型放射发光显微镜的定向传感器

• 批准号: 10324422
• 负责人: STUART R MILLER
• 金额: $ 25.89万
• 依托单位: RADIATION MONITORING DEVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-10 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10324422
• 关键词: 3-Dimensional; Address; Affect; Attenuated; Beta Particle; Biological; Biological Factors; Biological Markers; Cell Culture Techniques; Cells; Ceramics; Clinical Trials; Collaborations; Complex; Confocal Microscopy; Data; Deposition; Development; Diagnostic; Diagnostic Imaging; Disease; Environment; Extracellular Matrix; Film; Fluorescence Microscopy; Goals; Hypoxia; Image; Imaging Phantoms; In Situ; In Vitro; Incidence; Individual; Ions; Light; Measures; Medical Imaging; Medicine; Methods; Microscope; Microscopy; Modeling; Noise; Nutrient; Oncology; Optics; Organoids; Output; Oxygen; Patients; Performance; Phase; Photons; Physiology; Play; Positron-Emission Tomography; Pre-Clinical Model; Proliferating; Property; Radioisotopes; Radiolabeled; Research; Research Personnel; Resolution; Role; Sampling; Signal Transduction; Solid Neoplasm; Specimen; Spottings; Stromal Cells; System; Techniques; Technology; Therapeutic; Thick; Thinness; Tissue Model; Tissues; Tracer; Tumor-Derived; Universities; Visualization; cell behavior; cellular imaging; clinical imaging; clinically relevant; density; design; detector; high resolution imaging; imaging capabilities; imaging system; improved; innovation; innovative technologies; microfluidic technology; microscopic imaging; monolayer; neoplastic cell; neovasculature; next generation; novel; nutrient deprivation; particle; pre-clinical research; professor; quantum; radiotracer; reconstruction; sensor; technological innovation; temporal measurement; three dimensional cell culture; tomography; tool; tumor; uptake

Microphysiological tumor models (μPTM) are increasingly used for preclinical research due to their ability to closely simulate, in vitro, the physiology of solid tumors. With the advent of microfluidics technology, new methods have been introduced to grow tissues in 3D inside perfused chambers and precisely control biological factors, such as cells, nutrients and oxygen, at a spatial and temporal level. These models can incorporate 3D extracellular matrices (ECM) and perfusable neovasculature, both key components of solid tumors. Being optically transparent, they permit excellent visualization of live cells through advanced optical microscopy techniques. Radioluminescence microscopy (RLM) is a method that was developed to image clinical radiotracers in live cells with high spatial resolution. However, this method in its current form cannot be used to adequately image 3D cell cultures due to the loss of spatial resolution and lack of tomographic capabilities for imaging thick samples. The goal of this project is to develop a novel layered scintillator design for limited-angle tomographic imaging of 3D cell cultures and other in vitro tissues such as organoids and tumor-chips. The dual-layer scintillator will provide angular information that can be used for 3D reconstruction of radiotracer distribution in these thick samples. Thus, such a technological advance has the potential for widespread use in research and medicine using the arsenal of existing diagnostic and therapeutic radioisotopes. It could be used to bridge the gap between these emergent tumor models and clinical trials, which use PET biomarkers as disease endpoints. In addition, the technology could be used to characterize how properties specific to the 3D microenvironment surrounding microtumors could affect the uptake and retention of radiotracers. Higher spatial resolution will allow cells to be probed in situ, in dense tissue sections. These new capabilities will be critical to help researchers develop patient-derived tumor models that recapitulate the most salient features of solid tumors and can be imaged using clinically relevant PET tracers. The objective of this Phase I project is to demonstrate the feasibility of successfully fabricating thin layers of a highly dense transparent scintillator, separated by a layer of non-scintillating transparent material. This novel design enables visualization of two scintillation spots so that the angle of incidence can be estimated to provide limited-angle tomographic projections. This innovative design will provide the spatial resolution required for visualization of radiotracer uptake in 3D cell cultures, microtumors, and other thick specimens.

微生理肿瘤模型 (μPTM) 越来越多地用于临床前研究，因为它们能够 随着微流体技术的出现，在体外密切模拟实体瘤的生理学。 已经引入了在灌注室内以 3D 方式生长组织并精确控制生物的方法 这些模型可以包含空间和时间层面的因素，例如细胞、营养物质和氧气。 细胞外基质（ECM）和可灌注新血管系统是实体瘤的关键组成部分。 光学透明，它们可以通过先进的光学显微镜对活细胞进行良好的可视化 技术。 放射发光显微镜 (RLM) 是一种用于在活体中对临床放射性示踪剂进行成像的方法。 然而，当前形式的这种方法不能用于充分成像。 由于空间分辨率损失和缺乏厚层成像的断层扫描功能而导致 3D 细胞培养 该项目的目标是开发一种用于有限角度断层扫描的新型分层闪烁体设计。 3D 细胞培养物和其他体外组织（例如类器官和肿瘤芯片）的成像。 闪烁体将提供角度信息，可用于放射性示踪剂分布的 3D 重建 因此，这种技术进步有可能在研究和应用中得到广泛应用。 使用现有的诊断和治疗放射性同位素的药物可以用来弥合这一问题。 这些新兴肿瘤模型与使用 PET 生物标志物作为疾病终点的临床试验之间存在差距。 此外，该技术还可用于表征 3D 微环境特有的特性 周围的微肿瘤可能会影响放射性示踪剂的吸收和保留，更高的空间分辨率将允许。 这些新功能对于帮助研究人员至关重要。 开发源自患者的肿瘤模型，该模型概括了实体瘤最显着的特征，并且可以 使用临床相关 PET 示踪剂进行成像。 该第一阶段项目的目标是证明成功制造薄层的可行性 一种高密度透明闪烁体，由一层非闪烁透明材料隔开。 该设计能够使两个闪烁点可视化，从而可以估计入射角以提供 这种创新设计将提供有限角度断层扫描投影所需的空间分辨率。 3D 细胞培养物、微肿瘤和其他厚样本中放射性示踪剂摄取的可视化。