Apoptosis and Inflammation Imaging

描述（由候选人提供）： 该项目的目的是开发一种新的成像方法，细胞凋亡或程序性细胞死亡。程序性细胞死亡是一种调节过程，通常发生在体内，在此期间细胞响应某些触发而死亡，而不影响邻近的健康细胞。坏死是细胞死亡的另一种形式，当细胞突然受伤时发生，导致炎症和周围组织的广泛损伤。在许多疾病中，细胞死亡过多，例如在败血症中，通常保护性免疫细胞死亡，使患者没有有效的防御系统来对抗现有的感染，或者细胞死亡不足，例如在癌症中，生长的细胞对正常的细胞死亡触发没有反应。因此，开发新的成像技术将是有帮助的，该技术专门检测细胞凋亡以识别正在经历该过程的组织，并且可能对靶向该特定细胞死亡途径的治疗作出反应。该项目将重点评估两类新化合物，这些化合物特异性结合正在发生细胞凋亡的细胞，并可用于细胞死亡的正电子发射断层成像。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看到肿瘤是否对化疗有反应，如果需要，医生可以在一个周期后改变化疗治疗，而不必等到完成整个化疗过程。在脓毒症危重患者中，早期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，观察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伤之前确定治疗是否有效。

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.