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 8-1200 万美国人的主要临床问题，导致严重的死亡和残疾。靶向药物或基因疗法可能通过现有侧支动脉的血管重塑（动脉生成）和/或刺激微血管密度增加（血管生成）改善灌注，从而改善这些患者的临床症状。这些生物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。我们将描述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avb3整合素和一氧化氮（NO）在介导缺氧诱导的血管生成和血流诱导的动脉生成中的作用。目前的提案是对先前项目的竞争性更新，该项目旨在开发基于非侵入性放射性示踪剂的成像策略，以识别血管生成的缺氧刺激，并使用针对 avb3 整合素的放射性示踪剂直接评估血管生成。当前项目的主要目标是使用非侵入性混合 microSPECT/X 射线 CT 成像策略应用和完善这些方法，以体内评估 PAD 中血管生成和动脉生成的相互依赖作用，并探索 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来介导血管生成过程，并且由此导致的组织灌注增加和血管阻力降低导致血流介导的动脉生成增加。该项目将利用已建立的选择性结合 avb3 整合素的靶向放射性示踪剂，以及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的放射性示踪剂。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共同配准，而且有助于示踪剂摄取的量化。目前的应用直接建立在先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，对于 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