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: 8169409
• 负责人: Eva M. Sevick-Muraca
• 金额: $ 1.67万
• 依托单位: LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169409
• 关键词: Affinity; Animals; Binding; Biological; Cell surface; Cells; Chemicals; Clinical; Computer Retrieval of Information on Scientific Projects Database; Development; Diagnostic; Diagnostic Imaging; Disease; Drug Kinetics; Dyes; Exhibits; Fluorescence; Fluorescent Dyes; Fluorescent Probes; Funding; Grant; In Vitro; Injection of therapeutic agent; Institution; Label; Measurement; Measures; Noise; Peptides; Phase; Property; Research; Research Personnel; Resolution; Resources; Source; System; Toxic effect; Translations; United States National Institutes of Health; cancer cell; chromophore; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 临床使用探针的选择主要是有机荧光团，因为它们具有良好的毒性和药代动力学特性。 另外，有机染料可以很容易地与将与癌细胞受体结合的肽或其他功能组偶联。 有机荧光团也可以用与有关特定细胞具有高亲和力的送货车标记。 这些荧光探针的发展有助于诊断分子成像，并且通过设计最佳的化学，物理和疾病特异性特性来调节体内这些荧光团的特异性和延长摄取。 因此，当将荧光染料偶联到生物实体时，该染料的光物理特性可能会改变。 因此，这些NIR有机染料构建体的发展始于在小动物注射和临床翻译之前的体外诊断。 方法 NIR荧光团通常会彼此重叠或与体内发现的各种发色团重叠。 NIR中的自动荧光有助于增加背景噪声并减少目标对背景测量值。因此，在设计荧光探针时，重要的是选择具有最佳光谱特性的探针。 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）区分细胞上标记的物种以测量结合机制，（iii）检查的荧光物种是双标记用于多波长分子成像。 此外，相敏感流系统将用于（i）与细胞表面结合以与未结合的探针进行比较时，测量荧光构建体的寿命，（ii）检测相敏感的NIR荧光，并区分从细胞自动荧光的区分在荧光团结合细胞上，（iii）比较了具有相似发射光谱的竞争性细胞结合液体的寿命。