Tumor FDG Kinetics in a 3-D Tissue Culture System

3-D 组织培养系统中的肿瘤 FDG 动力学

• 批准号: 6824750
• 负责人: CHIN K NG
• 金额: $ 16.54万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6824750
• 关键词: adenocarcinoma; bioimaging /biomedical imaging; cell population study; deoxyglucose; glucose metabolism; glucose transport; hexokinase; neoplastic growth; nonsmall cell lung cancer; positron emission tomography; radionuclides; squamous cell carcinoma; three dimensional imaging /topography; tissue /cell culture

DESCRIPTION (provided by applicant): Positron Emission Tomography (PET) offers the uniqueness of non-invasive in vivo quantification for a variety of biological diseases. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) has shown great promises to be a powerful unique clinical tool for the diagnosis and the staging of many carcinomas, especially when it is used simultaneously with Computed Tomography (CT). Nonetheless, the validity of FDG as a radiotracer for glucose metabolism in cancer cells is still not well understood. In order to explore this further, four human non-small cell lung cancer (NSCLC) lines (squamous, adenocarcinoma, large cell, and bronchioalveolar) will be immobilized with microcarriers in suspension. This 3-D tissue culture system where cells are isolated from other control factors is analogous to an isolated perfused heart system. Time activity curves (TAC) will be obtained in high temporal resolution by on-line dynamic measurement of FDG uptake into cells with two external gamma probes. The TAC will be further analyzed by a compartmental model for kinetic parameters associated with both the transport and phosphorylation steps. Three specific aims for this proposal are: 1. To determine the growth conditions to obtain a steady state of immobilized cells per gram microcarrier for four common types of NSCLCs, 2. To characterize the metabolic and hemodynamic parameters (oxygen, glucose, lactate, CO2, pH, temperature) for all four cell types in the 3-D tissue culture system, 3. To investigate FDG kinetics and the lumped constant behaviour in all four cell types. Since the overexpression of glucose transporter and hexokinase isoforms are not expected to be the same for all carcinomas, FDG kinetics in these four NSCLCs should demonstrate certain degree of differential uptakes. Results obtained from the proposed research will provide a basis for the understanding of FDG kinetics in cancer cells and the identification of new non-invasive means to probe biological diseases. The same experimental setup can also be used with many other types of cells to probe biological diseases with either PET or SPECT ligands. FDG kinetics in NSCLCs was chosen only to demonstrate its potential utility by relating problems to a well-established clinical procedure in PET imaging. Therefore the long-term objective is to develop a versatile experimental setup that combines a 3-D tissue culture system with external gamma probes for the development and the evaluation of radiopharmaceuticals.

描述（由申请人提供）： 正电子发射断层扫描 (PET) 为多种生物疾病提供了独特的非侵入性体内定量方法。 F-18 标记的氟脱氧葡萄糖 (FDG) 的 PET 成像已显示出巨大的前景，有望成为许多癌症的诊断和分期的强大而独特的临床工具，特别是当它与计算机断层扫描 (CT) 同时使用时。尽管如此，FDG 作为癌细胞葡萄糖代谢放射性示踪剂的有效性仍不清楚。为了进一步探索这一点，四种人类非小细胞肺癌 (NSCLC) 系（鳞状细胞癌、腺癌、大细胞肺癌和支气管肺泡癌）将用悬浮微载体固定。这种 3D 组织培养系统将细胞与其他控制因子分离，类似于分离的灌注心脏系统。通过使用两个外部伽马探针在线动态测量细胞摄取的 FDG，可以获得高时间分辨率的时间活性曲线 (TAC)。 TAC 将通过区室模型进一步分析与运输和磷酸化步骤相关的动力学参数。该提案的三个具体目标是： 1. 确定四种常见类型 NSCLC 获得每克微载体固定化细胞稳定状态的生长条件， 2. 表征代谢和血流动力学参数（氧、葡萄糖、乳酸、CO2） 、pH、温度）适用于 3-D 组织培养系统中的所有四种细胞类型，3. 研究所有四种细胞类型中的 FDG 动力学和集总常数行为。由于葡萄糖转运蛋白和己糖激酶亚型的过度表达预计不会在所有癌症中都相同，因此这四种 NSCLC 中的 FDG 动力学应该表现出一定程度的差异吸收。从拟议的研究中获得的结果将为了解癌细胞中的 FDG 动力学和识别新的非侵入性手段来探测生物疾病提供基础。相同的实验装置还可用于许多其他类型的细胞，通过 PET 或 SPECT 配体探测生物疾病。选择 FDG 在 NSCLC 中的动力学只是为了通过将问题与 PET 成像中成熟的临床程序联系起来来证明其潜在效用。因此，长期目标是开发一种多功能实验装置，将 3D 组织培养系统与外部伽马探针相结合，用于放射性药物的开发和评估。