PET Imaging of Brain Tumor Angiogenesis and Antiangiogenic Treatment

脑肿瘤血管生成和抗血管生成治疗的 PET 成像

• 批准号: 7645573
• 负责人: XIAOYUAN CHEN
• 金额: $ 22.1万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7645573
• 关键词: Acceleration; Affinity; Angiogenesis Inhibitors; Apoptosis; Brain Neoplasms; Clinical; Drug Kinetics; Endothelial Cells; Fostering; Generations; Image; Imaging Techniques; Integrin alpha Chains; Integrins; Investigation; Lead; Lymphoma; Magnetic Resonance Imaging; Modeling; Molecular Structure; Monitor; Natural History; Peptides; Positron-Emission Tomography; Proteins; Range; Research Project Grants; Role; Series; Testing; Tracer; Translations; Treatment Efficacy; Tumor Angiogenesis; antiangiogenesis therapy; base; cancer therapy; cell motility; clinical application; hydrophilicity; molecular size; neoplastic cell; novel; prevent; radiotracer; receptor; receptor binding; response; tumor; tumor growth; uptake

Our long-range objectives are to develop PET imaging techniques for brain tumor imaging in order to identify molecular structures and receptors that are altered during brain tumor growth and spread and to help predict the natural history and response to therapy. The objective in this proposal is to image brain tumor angiogenesis and anti-angiogenic therapy efficacy by means of PET and MRI. Brain tumors are angiogenesis dependent. Anti-angiogenic therapies that either block expression of tumor angiogenesis related proteins or directly prevent endothelial cells from migration and induce apoptosis, have been proven effective in brain tumors. We have previously developed a series of cyclic RGB peptide radiotracers for PET imaging of brain tumor models based upon av-integrin antagonism. The tumor targeting efficacy and pharmacokinetics of the tracers are highly dependent on their receptor binding affinity, hydrophilicity, and molecular size, etc. This project will expand our investigations with aim to: (1) optimize the integrin specific PET tracers for clinical applicability; (2) correlate alpha-v integrin expression level with the magnitude of tumor (both tumor cells and rumor vasculature) tracer uptake; and (3) evaluate anti-integrin brain tumor treatment with a PET/MRI combination. Overall, this proposal will foster in a novel and unique way our understanding of brain tumor angiogenesis in relationship to alpha-v integrin expression and allow for direct assessment of anti-angiogenic treatment efficacy based upon alpha-integrin targeted PET imaging. This should lead to direct clinical translation of the PET probes validated and also allow imaging of angiogensis for other tumors (e.g., for lymphomas studied in Research Project 2). Furthermore it should help show the role of imaging to monitor anti-cancer therapies for acceleration of testing of new generation of anti-angiogenesis agents.

我们的远程目标是开发用于脑肿瘤成像的PET成像技术，以鉴定在脑肿瘤生长过程中改变并扩散并帮助预测自然史和对治疗的反应的分子结构和受体。该建议的目的是通过PET和MRI对脑肿瘤血管生成和抗血管生成疗法的功效进行图像。脑肿瘤取决于血管生成。抗血管生成的疗法可阻止肿瘤血管生成相关蛋白的表达或直接防止内皮细胞迁移并诱导凋亡，这在脑肿瘤中有效。我们以前已经开发了一系列基于AV-紧密拮抗作用的脑肿瘤模型的PET成像的环状RGB肽放射性示例。靶向肿瘤的功效和药代动力学 示踪剂高度取决于其受体结合亲和力，亲水性和分子大小等。该项目将扩大我们的研究，目的是：（1）优化整联蛋白特异性宠物示踪剂以临床适用性； （2）将α-V整合素表达水平与肿瘤的大小（肿瘤细胞和谣言脉管系统）相关联； （3）通过PET/MRI组合评估抗整合蛋白脑肿瘤的治疗。总体而言，该建议将以一种新颖而独特的方式促进我们对脑肿瘤血管生成与α-V整合素表达关系中的理解，并允许基于α-整合蛋白靶向的PET成像直接评估抗血管生成治疗功效。这应该导致对验证的PET探针的直接临床翻译，并允许对其他肿瘤进行血管生成成像（例如，研究研究项目2中研究的淋巴瘤）。此外，它应该有助于显示成像的作用以监视 抗癌疗法，用于加速新一代抗血管生成剂。