In vivo imaging of molecular targets

分子靶标的体内成像

• 批准号: 6563982
• 负责人: Robert J. Gillies
• 金额: $ 29.68万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563982
• 关键词: SCID mouse; androstane compound; angiogenesis inhibitors; annexins; antineoplastics; apoptosis; bioimaging /biomedical imaging; diagnosis design /evaluation; human subject; magnetic resonance imaging; neoplastic growth; noninvasive diagnosis; patient oriented research; pharmacokinetics; thalidomide

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.

描述（由申请人提供） 21世纪肿瘤学面临的挑战之一是 患者护理的个体化。肿瘤，即使是同一类型，也有广泛的 对标准和新颖的呈现范围和响应范围广泛 疗法。治疗前的基因分型在允许治疗方面显示出巨大的希望 针对个体患者的治疗选择。治疗开始后， 然而，非侵入性检测早期反应（或无反应）的方法 个体肿瘤的治疗对于总体目标很重要 改善对个别患者的护理。因此，响应者可以继续 治疗成功后无反应者可因治疗无效而停药 和毒性疗法并转向替代疗法。总体假设 因此，该项目指出，非侵入性成像方式可以监测 个别患者对治疗的反应。在当前的背景下 建议，非侵入性成像可以帮助开发和优化新的治疗方法 通过使用对代理端点高度敏感的代理端点 分子靶标。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。这 因此，该项目的具体目标是： 4.1 使用两种非侵入性成像方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， 两者均处于临床试验阶段。细胞凋亡是所有疾病的共同终点 该计划中使用的疗法。这将在两种动物中进行 模型和人类患者。 4.2 与使用 SU-5416 和沙利度胺的项目 3 合作，监测 使用动态对比增强对抗血管生成药物的治疗反应 磁共振成像 (DCE-MRI)。这将在动物模型和 人类患者。 4.3 与使用 DPIEL 和 Wortmannin 的项目 I 合作，使用非侵入性 磁共振波谱（MRS）来表征代谢 抑制剂治疗前后肿瘤模型的分子特征 的信号转导。这将在动物模型和 人类患者。