MicroPET and NIR Fluorescence Imaging Tumor Angiogenesis

MicroPET 和 NIR 荧光成像肿瘤血管生成

基本信息

批准号：
6799317
负责人：
XIAOYUAN CHEN
金额：
$ 23.56万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-15 至 2006-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6799317
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

项目摘要

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和技术，以识别癌前或癌细胞的血管生成特性，以预测临床过程和对干预的反应。最近已经确定，肿瘤的生长取决于血管生成，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的极大关注，因为它们可能为长期控制癌症提供了一种实际手段。成像可以在抗血管生成治疗的临床前发育和临床应用中起主要作用。整联蛋白alphavbeta3在静止血管中不容易检测到，但在血管生成血管和各种恶性人类肿瘤中高度表达，是影响肿瘤生长，局部侵入性和转移潜力的重要粘附受体。肿瘤血管生成可以通过用含有arg-gly-Asp（RGD）氨基酸序列的小肽拮抗α3整联蛋白来在体内阻塞。由于其高度限制的表达且在血管生成中的重要作用，因此alphavbeta3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疾病中alphavbeta3表达水平的能力对于靶向治疗的治疗计划至关重要。分子探针的全身优化用于评估肿瘤靶向功效以及体内药代动力学和药效动力学的系统性优化也将实现快速的药物筛查和新药物发现。在这个项目中，我们建议在不同实体瘤模型中开发一系列新的环状RGD肽探针，以用于微型网和肿瘤血管生成的光学成像。 AIM 1：用于胶质母细胞瘤模型的MicroPET成像和近红外荧光（NIRF）成像的标签环状RGD肽。 AIM 2：使用具有最佳肿瘤靶向功效和体内药代动力学的放射性示例和NIRF探针来对不同的实体瘤模型进行成像。我们预计，使用MicroPET和NIRF成像对Alphavbeta3表达和功能活性的无创系列研究将成为重要的工具，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未来的R01类型赠款。

项目成果

期刊论文数量（62）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Synthesis and crystal and molecular structure of a tetranuclear cluster based on the rhenium(III)-bisorganohydrazino core: [Re(HNNC(4)H(3)N(2))(NNC(4)H(3)N(2))(OCH(3))(2)](4).

基于铼(III)-双有机肼核的四核簇的合成、晶体和分子结构：[Re(HNNC(4)H(3)N(2))(NNC(4)H(3)N(2)

DOI：
10.1016/s0020-1693(00)00207-3
发表时间：
2000
期刊：
Inorganica chimica acta
影响因子：
2.8
作者：
Femia,FrankJ;Chen,Xiaoyuan;Maresca,KevinP;Babich,JohnW;Zubieta,Jon
通讯作者：
Zubieta,Jon

The syntheses and structures of '3+2' and '2+2+1' oxorhenium mixed-ligand complexes employing 8-hydroxy-5-nitroquinoline as the bidentate N,O donor ligand.

DOI：
10.1016/s0020-1693(00)00218-8
发表时间：
2000-10
期刊：
Inorganica chimica acta
影响因子：
2.8
作者：
Xiaoyuan Chen;Frank J. Femia;J. Babich;J. Zubieta
通讯作者：
Xiaoyuan Chen;Frank J. Femia;J. Babich;J. Zubieta

Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel.

DOI：
发表时间：
2007-03
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
0
作者：
A. Hsu;W. Cai;A. Veeravagu;K. Mohamedali;Kai Chen;Sehoon Kim;H. Vogel;Lewis C. Hou;V. Tse
通讯作者：
A. Hsu;W. Cai;A. Veeravagu;K. Mohamedali;Kai Chen;Sehoon Kim;H. Vogel;Lewis C. Hou;V. Tse

Structural characterizations of an Re(IV) complex [ReCl(4)(OPPh(3))(2)] and of an imino species [ReOCl(2)(PPh(3))(eta-OC(6)H(4)-2-CH=NH)] prepared from the reaction of [ReOCl(3)(PPh(3))(2)] with salicylaldoxime.

Re(IV) 配合物 [ReCl(4)(OPPh(3))(2)] 和亚氨基物质 [ReOCl(2)(PPh(3))(eta-OC(6)H(4) 的结构表征