SPECTRAL AND LIFETIME SHIFTS OF NIR DIAGNOSTIC IMAGING DYES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 临床使用的探针主要是有机荧光团，因为它们具有良好的毒性和药代动力学性质。此外，有机染料可以很容易地与多肽或其他官能团结合在一起，从而与癌细胞受体结合。有机荧光团也可以用对特定细胞具有高亲和力的递送载体来标记。这些荧光探针的发展促进了诊断分子成像，并通过设计最佳的化学、物理和疾病特异性属性来调节这些荧光团在体内的特定和长期摄取。因此，当荧光染料与生物实体结合时，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结构的开发从体外诊断开始，然后是小动物注射和临床翻译。 方法 近红外荧光团通常彼此重叠或与体内发现的各种发色团重叠。近红外光谱中的自发荧光增加了背景噪声，减少了目标对背景的测量。因此，在设计荧光探针时，选择具有最佳光谱性能的探针是很重要的。高分辨率光谱系统将用于(I)测量光谱和比较类似的有机染料以选择最佳的荧光团，(Ii)区分细胞上标记的物种以测量结合机制，以及(Iii)检查双标记的荧光物种以进行多波长分子成像。此外，相敏流动系统将被用于(I)测量结合到细胞表面的荧光结构的寿命，以便与未结合的探针进行比较，(Ii)检测相敏感的近红外荧光并将其与荧光团结合的细胞上的细胞自身荧光区分开来，以及(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。

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.