MicroPET and NIR Fluorescence Imaging Tumor Angiogenesis

MicroPET 和 NIR 荧光成像肿瘤血管生成

• 批准号: 6708437
• 负责人: XIAOYUAN CHEN
• 金额: $ 8.37万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6708437
• 关键词: angiogenesis; arginine; aspartate; bioimaging /biomedical imaging; biomarker; biotechnology; fluorescence spectrometry; glioblastoma multiforme; glycine; infrared radiation; infrared spectrometry; integrins; laboratory mouse; neoplasm /cancer blood supply; positron emission tomography; technology /technique development

DESCRIPTION (provided by applicant): Our long-term objective is to develop and validate new imaging markers and techniques that identify the angiogenic properties of precancerous or cancerous cells that will predict clinical course and response to intervention. It has been recently established that tumor growth is angiogenesis dependent, and there is a specific correlation between blood vessel density in cancers and their metastatic potential. Anti-angiogenic therapy aimed at blocking new blood vessel growth in tumors is of great interest, since they may provide a practical means for long-term control of cancer. Imaging can play a major role in the pre-clinical development and clinical application of anti-angiogenic therapy. Integrin alphavbeta3, which is not readily detectable in quiescent vessels but becomes highly expressed in angiogenic vessels and various malignant human tumors, is an important adhesion receptor affecting tumor growth, local invasiveness, and metastatic potential. Tumor angiogenesis can be blocked in vivo by antagonizing the alphavbeta3 integrin with small peptides containing the Arg-Gly-Asp (RGD) amino acid sequence. Because of its highly restricted expression and its vital role in angiogenesis, the alphavbeta3 integrin is an attractive candidate in anticancer therapy. The ability to quantify the alphavbeta3 expression level in tumors and other angiogenesis related diseases is of vital importance for therapeutic planning of alphavbeta3 targeted therapy. Systemic optimization of molecular probes for evaluation of tumor targeting efficacy as well as in vivo pharmacokinetics and pharmacodynamics will also enable rapid drug screening and new drug discovery. In this project we propose to develop a series of new cyclic RGD peptide based probes for microPET and optical imaging of tumor angiogenesis in different solid tumor models. Aim 1: label cyclic RGD peptides for microPET imaging and near-infrared fluorescence (NIRF) imaging of glioblastoma model. Aim 2: Apply the radiotracers and NIRF probes with optimal tumor targeting efficacy and in vivo pharmacokinetics to image different solid tumor models. We anticipate that noninvasive serial studies of alphavbeta3 expression and functional activity using microPET and NIRF imaging will become important tools complementary each other to evaluate the role of alphavbeta3 integrin during tumor progression and metastasis. All the results obtained here will be used for future application of a R01 type grant.

描述（由申请人提供）：我们的长期目标是开发和验证新的成像标记物和技术，识别癌前或癌细胞的血管生成特性，从而预测临床病程和对干预的反应。最近已经确定肿瘤生长依赖于血管生成，并且癌症中的血管密度与其转移潜力之间存在特定的相关性。旨在阻止肿瘤中新血管生长的抗血管生成疗法引起了人们极大的兴趣，因为它们可能为长期控制癌症提供实用手段。影像学在抗血管生成治疗的临床前开发和临床应用中可以发挥重要作用。整合素αvβ3在静止血管中不易检测到，但在血管生成血管和各种人类恶性肿瘤中高度表达，是影响肿瘤生长、局部侵袭性和转移潜力的重要粘附受体。通过用含有 Arg-Gly-Asp (RGD) 氨基酸序列的小肽拮抗 alphavbeta3 整联蛋白，可以在体内阻断肿瘤血管生成。由于其高度受限的表达及其在血管生成中的重要作用，αvβ3整合素是抗癌治疗中有吸引力的候选者。量化肿瘤和其他血管生成相关疾病中 alphavbeta3 表达水平的能力对于 alphavbeta3 靶向治疗的治疗计划至关重要。用于评估肿瘤靶向功效以及体内药代动力学和药效学的分子探针的系统优化也将使得快速药物筛选和新药发现成为可能。在这个项目中，我们建议开发一系列基于环状 RGD 肽的新型探针，用于不同实体瘤模型中肿瘤血管生成的 microPET 和光学成像。目标 1：标记环状 RGD 肽，用于胶质母细胞瘤模型的 microPET 成像和近红外荧光 (NIRF) 成像。目标2：应用具有最佳肿瘤靶向功效和体内药代动力学的放射性示踪剂和NIRF探针对不同实体瘤模型进行成像。我们预计，使用 microPET 和 NIRF 成像对 alphavbeta3 表达和功能活性进行无创系列研究将成为相互补充的重要工具，以评估 alphavbeta3 整合素在肿瘤进展和转移过程中的作用。此处获得的所有结果将用于将来申请 R01 类型补助金。