SPECTRAL AND LIFETIME SHIFTS OF NIR DIAGNOSTIC IMAGING DYES

近红外诊断成像染料的光谱和寿命变化

• 批准号: 8361773
• 负责人: Eva M. Sevick-Muraca
• 金额: $ 1.12万
• 依托单位: LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361773
• 关键词: Affinity; Animals; Binding; Biological; Cell surface; Cells; Chemicals; Clinical; Development; Diagnostic; Diagnostic Imaging; Disease; Drug Kinetics; Dyes; Exhibits; Flow Cytometry; Fluorescence; Fluorescent Dyes; Fluorescent Probes; Funding; Grant; In Vitro; Injection of therapeutic agent; Label; Measurement; Measures; National Center for Research Resources; Noise; Peptides; Phase; Principal Investigator; Property; Research; Research Infrastructure; Resolution; Resources; Sorting - Cell Movement; Source; System; Toxic effect; Translations; United States National Institutes of Health; cancer cell; chromophore; cost; design; fluorophore; functional group; in vivo; molecular imaging; receptor; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The choice of probes for clinical use is primarily organic fluorophores because of their favorable toxicity and pharmacokinetic properties. Additionally, organic dyes can be easily conjugated to peptides or other functional groups that will bind to cancer cell receptors. Organic fluorophores may also be tagged with a delivery vehicle that has high affinity to a particular cell in question. The development of these fluorescent probes facilitates diagnostic molecular imaging, and the specific and prolonged uptake of these fluorophores in the body is modulated by designing optimum chemical, physical and thus disease-specific properties. Accordingly, when a fluorescent dye is conjugated to a biological entity the photophysical properties of that dye may change. Therefore the development of these NIR organic dye constructs begins with in vitro diagnostics prior to small animal injection and clinical translation. Approach NIR fluorophores often have overlapping spectra either with each other or with various chromophores found in vivo. Autofluorescence in the NIR contributes to increased background noise and reduced target-to-background measurements. When designing a fluorescent probe it is thus important to select one with optimum spectral properties. The high-resolution spectral system will be used to (i) measure spectra and compare similar organic dyes to select the optimum fluorophore, (ii) distinguish between labeled species on the cell for measuring binding mechanisms, and (iii) examine fluorescent species that are dual-labeled for multi-wavelength molecular imaging. Additionally, the phase-sensitive flow system will be used to (i) measure the lifetime of fluorescent constructs when bound to cell surfaces for comparison to the un-bound probe, (ii) detect phase-sensitive NIR fluorescence and discriminate that from cellular autofluorescence on fluorophore bound cells, and (iii) compare the lifetimes of competitive cell-bound fluophores exhibiting similar emission spectra.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 临床使用的探针主要选择有机荧光团，因为它们具有良好的毒性和药代动力学特性。 此外，有机染料可以很容易地与肽或其他能与癌细胞受体结合的官能团结合。 有机荧光团也可以用与所讨论的特定细胞具有高亲和力的递送载体来标记。 这些荧光探针的开发促进了诊断分子成像，并且通过设计最佳的化学、物理以及疾病特异性特性来调节这些荧光团在体内的特异性和长期摄取。 因此，当荧光染料与生物实体缀合时，该染料的光物理性质可能会改变。 因此，这些近红外有机染料构建体的开发始于小动物注射和临床转化之前的体外诊断。 方法 NIR 荧光团通常具有彼此重叠的光谱或与体内发现的各种发色团重叠的光谱。近红外中的自发荧光会增加背景噪声并减少目标到背景的测量。因此，在设计荧光探针时，选择具有最佳光谱特性的探针非常重要。 高分辨率光谱系统将用于（i）测量光谱并比较类似的有机染料以选择最佳荧光团，（ii）区分细胞上的标记物质以测量结合机制，以及（iii）检查双标记用于多波长分子成像。 此外，相敏流系统将用于 (i) 测量荧光构建体与细胞表面结合时的寿命，以便与未结合的探针进行比较，(ii) 检测相敏 NIR 荧光并将其与细胞自发荧光区分开来(iii) 比较具有相似发射光谱的竞争性细胞结合荧光团的寿命。