Apoptosis and Inflammation Imaging

细胞凋亡和炎症成像

• 批准号: 7678910
• 负责人: Delphine L Chen
• 金额: $ 16.68万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7678910
• 关键词: Affect; Aftercare; Animal Disease Models; Apoptosis; Apoptotic; Binding; Caring; Caspase; Cell Death; Cells; Cessation of life; Clinical; Critical Illness; Diagnosis; Disease; Enzymes; Evaluation; Extracellular Space; Gold; Hand; Image; Imaging Techniques; Immune; Infection; Inflammation; Inflammatory; Inflammatory Response; Inhibition of Apoptosis; Injury; Isatin; Isotopes; Label; Left; Liver; Malignant Neoplasms; Measurement; Measures; Membrane; Methods; Modeling; Necrosis; Neurodegenerative Disorders; Neurons; Noise; Normal Cell; Organ; Pathway interactions; Patients; Physicians; Positron; Positron-Emission Tomography; Process; Radiolabeled; Rodent; Sepsis; Signal Transduction; Spleen; Staining method; Stains; System; Thymus Gland; Tissues; Tracer; Work; annexin A5; caspase-3; chemotherapy; dosimetry; fighting; imaging modality; in vivo; injured; nonhuman primate; radiotracer; response; standard measure; technique development; tumor; uptake

DESCRIPTION (provided by candidate): The purpose of this project is to develop a new method of imaging apoptosis, or programmed cell death. Programmed cell death is a regulated process that occurs normally within the body during which cells die in response to certain triggers without affecting neighboring healthy cells. Necrosis, another form of cell death, occurs when cells have been suddenly injured, leading to inflammation and extensive damage to surrounding tissues as a result. In many diseases there is either an excess of cell death, such as in sepsis where normally protective immune cells die, leaving the patient without an effective defense system to fight off the existing infection, or there is inadequate cell death, such as in cancer in which growing cells do not respond to normal cell death triggers. Therefore, it would be helpful to develop new imaging techniques which detect apoptosis specifically to identify tissues that are undergoing this process and would likely respond to treatments targeting this particular cell death pathway. This project will focus on the evaluation of two new classes of compounds that bind specifically in cells undergoing apoptosis and that can be used for positron emission tomographic imaging of cell death. The development of this technique for imaging cell death will have multiple clinical uses in helping physicians diagnose and treat disease. For example, this imaging technique may allow physicians to see whether a tumor responded to chemotherapy or not earlier, allowing the physician to change the chemotherapy treatment after just one cycle if needed instead of having to wait until finishing the entire chemotherapy course. In critically ill patients with sepsis, identifying the presence of severe apoptosis early may allow physicians to identify patients that need more aggressive care before organs begin failing. In neurodegenerative diseases, seeing how many neurons are dying may also help identify people who need more aggressive treatment and may also help physicians determine whether a treatment is working or not, again before significant damage occurs.

描述（由候选人提供）： 该项目的目的是开发一种对细胞凋亡或程序性细胞死亡进行成像的新方法。程序性细胞死亡是一种在体内正常发生的受调节过程，在此过程中细胞响应某些触发因素而死亡，而不影响邻近的健康细胞。坏死是细胞死亡的另一种形式，当细胞突然受伤时就会发生坏死，从而导致炎症和周围组织的广泛损伤。在许多疾病中，要么细胞死亡过多，例如脓毒症，通常具有保护作用的免疫细胞死亡，使患者没有有效的防御系统来抵抗现有的感染，要么细胞死亡不足，例如癌症中的细胞死亡。生长中的细胞不会对正常的细胞死亡触发因素做出反应。因此，开发新的成像技术来特异性检测细胞凋亡，以识别正在经历这一过程的组织，并可能对针对这一特定细胞死亡途径的治疗做出反应，将是有帮助的。该项目将重点评估两类新化合物，它们特异性结合正在凋亡的细胞，并可用于细胞死亡的正电子发射断层扫描成像。这种细胞死亡成像技术的发展将在帮助医生诊断和治疗疾病方面具有多种临床用途。例如，这种成像技术可以让医生更早地了解肿瘤是否对化疗有反应，从而允许医生在需要时仅在一个周期后改变化疗治疗方案，而不必等到完成整个化疗疗程。在脓毒症危重患者中，尽早识别严重细胞凋亡的存在可能使医生能够在器官开始衰竭之前识别出需要更积极护理的患者。在神经退行性疾病中，了解有多少神经元正在死亡也可能有助于识别需要更积极治疗的人，也可能有助于医生在发生重大损害之前确定治疗是否有效。