Directional sensor for radioluminescence microscopy of next-generation tumor models

微生理学肿瘤模型（μPTM）越来越多地用于临床前研究，因为它们能够 在体外紧密模拟实体肿瘤的生理学。随着微流体技术的出现， 已经引入了在灌注室内3D生长组织并精确控制生物学的方法， 在空间和时间层面上，这些因素包括细胞、营养物质和氧气。这些模型可以包含3D 细胞外基质（ECM）和可灌注的新血管，两者都是实体瘤的关键组分。被 光学透明，它们允许通过先进的光学显微镜观察活细胞 技术. 放射性发光显微镜（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。 具有高空间分辨率的细胞。然而，该方法在其当前形式下不能用于充分地成像。 3D细胞培养由于空间分辨率的损失和缺乏成像厚的层析成像能力， 样品本计画的目标是发展一种新颖的分层闪烁体设计，用于有限角度断层摄影 3D细胞培养物和其他体外组织（如类器官和肿瘤芯片）的成像。双层 闪烁体将提供角度信息，该角度信息可用于放射性示踪剂分布的3D重建， 这些厚的样品。因此，这种技术进步有可能广泛用于研究， 使用现有的诊断和治疗放射性同位素的军火库的医学。它可以用来连接 这些新出现的肿瘤模型与使用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，该技术可用于表征3D微环境的特定特性 周围的微小肿瘤可能会影响放射性示踪剂的摄取和保留。更高的空间分辨率将允许 在致密组织切片中原位探测细胞。这些新功能对于帮助研究人员 开发患者来源的肿瘤模型，这些模型概括了实体瘤的最显著特征， 使用临床相关的PET示踪剂成像。 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。这本小说 该设计使得能够可视化两个闪烁点，使得可以估计入射角， 有限角度断层摄影投影。这一创新设计将提供所需的空间分辨率， 3D细胞培养物、微小肿瘤和其他厚标本中放射性示踪剂摄取的可视化。

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.