Directional sensor for radioluminescence microscopy of next-generation tumor models

微生理学肿瘤模型(μptm)因其在临床前研究中的能力而日益受到重视。 在体外，紧密模拟实体肿瘤的生理学。随着微流控技术的出现，新的 已经介绍了在3D灌流室内生长组织和精确控制生物的方法 因素，如细胞、营养物质和氧气，在空间和时间层面上。这些模型可以结合3D 细胞外基质(ECM)和可灌流的新生血管，这两个实体肿瘤的关键成分。存在 光学透明，它们允许通过先进的光学显微镜对活细胞进行出色的可视化 技巧。 放射发光显微镜(Rlm)是一种对临床放射性示踪剂进行活体成像的方法。 具有高空间分辨率的单元。然而，目前形式的这种方法不能用来充分地成像 3D细胞培养由于空间分辨率的丧失和缺乏成像厚度的断层扫描能力 样本。本项目的目标是开发一种用于有限角度层析成像的新型分层闪烁体设计。 3D细胞培养和其他体外组织的成像，如有机物和肿瘤芯片。双层结构 闪烁体将提供角度信息，可用于放射性示踪剂分布的三维重建 这些厚厚的样本。因此，这种技术进步有可能在研究和开发中广泛使用。 使用现有诊断和治疗放射性同位素武器库的医学。它可以用来架起 这些新出现的肿瘤模型和使用PET生物标记物作为疾病终点的临床试验之间存在差距。 此外，这项技术还可以用来表征3D微环境特有的特性 周围的微小肿瘤会影响放射性示踪剂的摄取和滞留。更高的空间分辨率将允许 在致密的组织切片中原位探测细胞。这些新功能将对帮助研究人员 开发患者衍生的肿瘤模型，概括实体肿瘤的最显著特征，并可以 使用临床相关的PET示踪剂进行成像。 这个第一阶段项目的目标是证明成功地制造薄层的可行性 一种高密度的透明闪烁体，由一层不闪烁的透明材料隔开。这部小说 设计使两个闪光点可视化，从而可以估计入射角以提供 有限角度层析投影。这种创新的设计将提供所需的空间分辨率 3D细胞培养、微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.