Synthesis of shortwave infrared flavylium polymethine dyes for improved biomedical imaging

项目摘要/摘要 生物医学成像是临床诊断的基本手段。普通成像 磁共振成像(MRI)、X射线成像和正电子发射等方式 层析成像(PET)受到成本、获取时间和/或电离辐射使用的限制。 荧光成像是生物医学成像的最佳方式，因为它是非侵入性的， 价格低廉，对生命系统来说是安全的。目前，荧光成像使用的是近红外光 (近红外，700-1000 nm)，但短波红外区(SWIR，1000-2000 nm) 电磁光谱已成为荧光成像的优势区域。 优点，如减少光散射和增加组织穿透率，这些较低的 能量光子，导致与NIR和驱动器形成鲜明对比的大幅增加 SWIR荧光团的创新。我们的团队最近开发了一种基于黄素基的光亮SWIR 多亚胺染料，名为Fram7。然而，不断增长的领域将受益于更光明和 深红移的荧光团。为了微调黄试剂染料以获得有效的活体成像 系统，结构变化和相应的光物理性质的研究是 这是必要的。通过对Flav7支架的系统衍生化，这项工作试图阐明 短波红外F-ӧ激光共振能量转移(FRET)圈的设计原理 在探测中。FRET探头对成像非常感兴趣，因为它们可以导致更大的信号到 噪声比与自由染料的比较。我们实验室的目标是招募SWIR FRET对进行改进 生物医学成像应用。使用先例的蛋白水解酶可裂解连接物，我们将 合成一种用于小组织肉瘤手术的SWIR FRET探头。这个 基于组织穿透型SWIR光的FRET探头的研制将极大地提高临床水平 诊断。

Project Summary/Abstract Biomedical imaging is an essential modality used in clinical diagnosis. Common imaging modalities such as magnetic resonance imaging (MRI), X-ray imaging, and positron emission tomography (PET), are constrained by cost, acquisition time, and/or use of ionizing radiation. Fluorescence imaging is an optimal modality for biomedical imaging, as it is non-invasive, inexpensive, and safe for living systems. Presently, fluorescence imaging uses near-infrared light (NIR, 700–1000 nm), but the shortwave infrared region (SWIR, 1000–2000 nm) of the electromagnetic spectrum has emerged as a superior region for fluorescence imaging. Advantages such as the reduced light scattering and increased tissue penetration of these lower energy photons, leads to dramatic increases in contrast compared to the NIR and drives innovation for SWIR fluorophores. Our group recently developed a bright flavylium-based SWIR polymethine dye named Flav7. However, the growing field would benefit from even brighter and deeply red-shifted fluorophores. In order to fine-tune flavylium dyes for effective imaging in living systems, an investigation of structural changes and corresponding photophysical properties is necessary. Through systematic derivatization of the Flav7 scaffold, this work seeks to elucidate design principles for the development of a SWIR Fӧrster resonance energy transfer (FRET) turn- on probe. FRET probes are of great interest for imaging as they can lead to greater signal-to- noise ratios compared to free dyes. Our lab aims to recruit SWIR FRET pairs for improved biomedical imaging applications. Using a precedented protease cleavable linker, we will synthesize a SWIR FRET probe for image guided surgery of small tissue sarcoma (STS). The development of a FRET probe reliant on tissue-penetrating SWIR light will greatly improve clinical diagnosis.