In vivo imaging of molecular targets

说明（申请人提供） 肿瘤学在21世纪世纪面临的挑战之一是 个性化的病人护理。即使是同一类型的肿瘤， 一系列的介绍和广泛的反应，无论是标准的和新的 治疗在治疗前进行基因分型显示出很大的希望， 为个别患者选择治疗方法。治疗开始后， 然而，非侵入性检测早期反应（或无反应）的方法 个体肿瘤的治疗对整体目标很重要， 改善对个别患者的护理。因此，响应者可以继续 治疗成功后，无应答者可因无效而中止治疗。 和毒性治疗，并转向替代疗法。总体假设 因此，该项目的研究表明，非侵入性成像方式可以监测 个体患者对治疗的反应。在系统帐户的上下文中 建议，非侵入性成像可以帮助开发和优化新的治疗方法 代理人通过使用替代端点是高度敏感的， 分子靶目前可用的成像方法允许终点 评估治疗效果，这些将有助于评估 临床前和临床环境中的治疗方案。附加成像 光谱方法将允许更直接地评估近端 药物作用的分子后果，这些将被开发。的 因此，该项目的具体目标是： 4.1 为了使用两种非侵入性成像模式监测体内细胞凋亡， 锝标记的膜联蛋白V成像和扩散磁共振成像， 这两种药物都在临床试验中。细胞凋亡是所有癌症的共同终点。 在这个项目中使用的疗法。这将在两种动物中进行 模型和人类患者。 4.2 与项目3合作，使用SU-5416和沙利度胺，监测 使用动态对比增强的抗血管生成药物的治疗反应 磁共振成像（DCE-MRI）。这将在两种动物模型中进行， 人类病人 4.3 与使用DPIEL和Wortmannin的项目I合作， 磁共振波谱（MRS），以表征代谢 用抑制剂治疗前后肿瘤模型的分子特征 信号转导的过程。这将在两种动物模型中进行， 人类病人

Description (provided by applicant) One of the challenges facing oncology in the 21st century is the individualization of patient care. Tumors, even of the same type, have a wide range of presentation and a wide range of responses to both standard and novel therapies. Genotyping prior to therapy is showing great promise in allowing a choice of therapies for individual patients. After treatment has begun, however, methods to non-invasively detect the early response (or non-response) of individual tumors to therapy would be important to the overall goal of improved care for the individual patient. Hence, responders could be continued on successful therapy, and non-responders could be discontinued on ineffective and toxic therapy and moved to alternative therapies. The overall hypothesis of this project thus states that non-invasive imaging modalities can monitor the response of individual patients to therapy. In the context of the current proposal, non-invasive imaging can help develop and optimize novel therapeutic agents through the use of surrogate endpoints that are highly sensitive to the molecular target. Imaging methods are currently available which allow end-point assessment of therapeutic efficacy and these will be useful in assessing treatment protocols in pre-clinical and clinical settings. Additional imaging and spectroscopic methods will allow more direct assessment of proximal molecular consequences of drug action, and these will be developed. The specific aims of this Project are therefore: 4.1 To monitor apoptosis in vivo using two non-invasive imaging modalities, Technetium-labeled Annexin V Imaging and diffusion Magnetic Resonance Imaging, which are both in clinical trials. Apoptosis is a common endpoint for all of the therapies used in this program. This will be performed in both animal models and in human patients. 4.2 In collaboration with project 3 using SU-5416 and thalidomide, to monitor therapeutic response to anti-angiogenic drugs using dynamic contrast-enhanced MR Imaging (DCE-MRI). This will be performed in both animal models and in human patients. 4.3 In collaboration with project I using DPIEL and Wortmannin, to use non-invasive magnetic resonance spectroscopy (MRS) to characterize the metabolic molecular signatures of tumor models before and after therapy with inhibitors of signal transduction. This will be performed in both animal models and in human patients.