Hybrid Imaging of Angiogenesis and Arteriogenesis

血管生成和动脉生成的混合成像

• 批准号: 7820934
• 负责人: Albert J Sinusas
• 金额: $ 2.32万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7820934
• 关键词: American; Angiography; Apoptosis; Arteries; Arts; Binding; Biological; Biological Process; Blood Vessels; Cell Adhesion; Cell Communication; Cell Proliferation; Cell Surface Receptors; Cell physiology; Cells; Clinical; Contrast Media; Development; Endothelial Cells; Evaluation; Family; Future; Goals; Hindlimb; Hybrids; Hypoxia; Image; Integrins; Ischemia; Limb Salvage; Mechanics; Mediating; Mediator of activation protein; Medical; Methodology; Modeling; Mus; Myocardial; Myocardial perfusion; Nitric Oxide; Operative Surgical Procedures; Patients; Perfusion; Peripheral arterial disease; Physiological; Process; Proliferation Marker; Quantitative Evaluations; Regional Perfusion; Regulation; Relative (related person); Research; Research Personnel; Role; Skeletal Muscle; Stimulus; Structure; System; Testing; Tissues; Tracer; Validation; Vascular remodeling; Vascular resistance; Wild Type Mouse; X-Ray Computed Tomography; analog; angiogenesis; attenuation; base; cell type; clinically relevant; density; disability; gene therapy; human NOS3 protein; improved; in vivo; inhibitor/antagonist; interest; migration; mortality; novel; programs; radiotracer; uptake

DESCRIPTION (provided by applicant): Peripheral arterial disease (PAD) is a major clinical problem afflicting 8-12 million Americans, and causes significant mortality and disability. Targeted medical or genetic therapies might provide clinical improvement of these patients through improved perfusion via vascular remodeling of existing collateral arteries (arteriogenesis) and/or by stimulating increased microvascular density (angiogenesis). There is an important interrelationship between these biological processes, however, it remains uncertain whether angiogenesis or arteriogenesis is the principal mediator of physiological improvement. We will characterize the interplay of these processes, in particular defining the role of avb3 integrins and nitric oxide (NO) in mediating hypoxia- induced angiogenesis and flow-induced arteriogenesis using well established murine models of hindlimb ischemia. The current proposal is a competitive renewal of a project previously directed at development of non-invasive radiotracer-based imaging strategies for identification of the hypoxic stimulus for angiogenesis, and direct evaluation of angiogenesis using radiotracers targeted at the avb3 integrin. A principal goal of the current project is to apply and refine these methodologies using non-invasive hybrid microSPECT/X-ray CT imaging strategies for the in vivo evaluation of the interdependent roles of angiogenesis and arteriogenesis in PAD, and to explore the role of NO in the regulation of integrins expressed on cells that mediate these processes. We hypothesize that ischemia may mediate the angiogenic process through regulation of integrins on several cell types, and that the resulting increases in tissue perfusion and decreases in vascular resistance result in increased flow-mediated arteriogenesis. The project will take advantage of established targeted radiotracers that selectively bind to the avb3 integrin, along with radiotracers that will track physiological changes in tissue perfusion and hypoxia associated with angiogenesis and arteriogenesis. The hybrid microSPECT/CT imaging system not only permits co-registration of biological images with developing vascular structures but facilitates quantification of tracer uptake. The current application builds directly on the novel imaging approaches previously developed, and will take advantage of established models of ischemia- and flow-induced angiogenesis to the study a critical mechanism of angiogenesis and arteriogenesis with potentially important clinical implications for evaluation and management of patients with PAD.

描述（由申请人提供）：外周动脉疾病（PAD）是困扰800 - 1200万美国人的主要临床问题，并导致显著的死亡率和残疾。靶向药物或遗传疗法可通过经由现有侧支动脉的血管重塑（动脉生成）和/或通过刺激增加的微血管密度（血管生成）改善灌注来提供这些患者的临床改善。这些生物学过程之间存在重要的相互关系，然而，血管生成或动脉生成是否是生理改善的主要介质仍不确定。我们将表征这些过程的相互作用，特别是使用完善的后肢缺血小鼠模型来定义avb 3整联蛋白和一氧化氮（NO）在介导缺氧诱导的血管生成和流动诱导的动脉生成中的作用。目前的建议是一个有竞争力的更新项目，以前针对开发的非侵入性放射性示踪剂为基础的成像策略，以确定缺氧刺激血管生成，并直接评估血管生成使用放射性示踪剂靶向的avb 3整合素。目前的项目的主要目标是应用和完善这些方法，使用非侵入性混合microSPECT/X射线CT成像策略，在体内评价血管生成和动脉生成在PAD中的相互依赖的作用，并探讨NO在调节介导这些过程的细胞上表达的整合素中的作用。我们假设缺血可能通过调节几种细胞类型上的整合素介导血管生成过程，并且由此导致的组织灌注增加和血管阻力降低导致流量介导的动脉生成增加。该项目将利用已建立的选择性结合avb 3整合素的靶向放射性示踪剂，沿着放射性示踪剂将跟踪与血管生成和动脉生成相关的组织灌注和缺氧的生理变化。混合microSPECT/CT成像系统不仅允许生物图像与发育中的血管结构的共配准，而且便于示踪剂摄取的量化。目前的应用直接建立在以前开发的新型成像方法的基础上，并将利用已建立的缺血和血流诱导的血管生成模型来研究血管生成和动脉生成的关键机制，这对PAD患者的评估和管理具有潜在的重要临床意义。

项目成果

New approach to quantification of molecularly targeted radiotracer uptake from hybrid cardiac SPECT/CT: methodology and validation.

混合心脏 SPECT/CT 中分子靶向放射性示踪剂摄取的定量新方法：方法学和验证。

• DOI: 10.2967/jnumed.113.123208
• 发表时间: 2013
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Li,Shimin;Sinusas,AlbertJ;Dobrucki,LawrenceW;Liu,Yi-Hwa
• 通讯作者: Liu,Yi-Hwa

Approaches to multimodality imaging of angiogenesis.

血管生成的多模态成像方法。

• DOI: 10.2967/jnumed.109.074963
• 发表时间: 2010
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Dobrucki,LawrenceW;deMuinck,EboD;Lindner,JonathanR;Sinusas,AlbertJ
• 通讯作者: Sinusas,AlbertJ

Imaging of matrix metalloproteinase activation and left ventricular remodeling.

基质金属蛋白酶激活和左心室重塑的成像。

• DOI: 10.1007/bf02938340
• 发表时间: 2007
• 期刊: Current cardiology reports
• 影响因子: 3.7
• 作者: Chung,Grace;Sinusas,AlbertJ
• 通讯作者: Sinusas,AlbertJ

Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging.

• DOI: 10.1016/j.yjmcc.2009.10.008
• 发表时间: 2010-06
• 期刊: Journal of molecular and cellular cardiology
• 影响因子: 5
• 作者: Dobrucki LW;Tsutsumi Y;Kalinowski L;Dean J;Gavin M;Sen S;Mendizabal M;Sinusas AJ;Aikawa R
• 通讯作者: Aikawa R

New molecular imaging targets to characterize myocardial biology.

• DOI: 10.1016/j.ccl.2008.12.008
• 发表时间: 2009-05
• 期刊: Cardiology clinics
• 影响因子: 2.4
• 作者: Morrison AR;Sinusas AJ
• 通讯作者: Sinusas AJ