Synthesis of shortwave infrared flavylium polymethine dyes for improved biomedical imaging

合成短波红外黄鎓聚次甲基染料以改善生物医学成像

• 批准号: 10494067
• 负责人: Anthony Spearman
• 金额: $ 4.12万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10494067
• 关键词: Attention; Biological; Cathepsins; Clinical; Development; Diagnosis; Disease Marker; Dyes; Electromagnetics; Electrons; Fluorescence; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Goals; Hand; Image; Image-Guided Surgery; In Vitro; Investigation; Ionizing radiation; Knowledge; Lead; Light; Location; Magnetic Resonance Imaging; Modality; Modification; Mus; Names; Noise; Organism; Penetration; Peptide Hydrolases; Peptides; Photons; Positioning Attribute; Positron-Emission Tomography; Property; Research; Signal Transduction; Soft tissue sarcoma; Structure; System; Time; Tissues; Work; X-Ray Medical Imaging; absorption; base; biomedical imaging; carboxypeptidase C; chromophore; clinical diagnosis; clinical imaging; cost; design; experimental study; fluorescence imaging; fluorophore; high resolution imaging; imaging modality; imaging probe; improved; in vivo; innovation; interest; light scattering; optical spectra; quantum; real-time images; recruit; sarcoma; scaffold; trend

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.

项目总结/摘要 生物医学成像是临床诊断中使用的基本模式。共成像 磁共振成像（MRI）、X射线成像和正电子发射等模态 断层扫描（PET）受到成本、采集时间和/或电离辐射的使用的限制。 荧光成像是生物医学成像的最佳模式，因为它是非侵入性的， 价格低廉，对生命系统安全。目前，荧光成像使用近红外光 (NIR，700-1000 nm），但是，短波红外区域（SWIR，1000-2000 nm）的 电磁光谱已经成为荧光成像的上级区域。 这些较低的光散射的优点，例如减少的光散射和增加的组织穿透， 能量光子，导致对比度与NIR相比显著增加， SWIR荧光团的创新。我们的团队最近开发了一种明亮的基于黄鎓的SWIR 多甲川染料，名为Flav 7。然而，不断增长的领域将受益于更明亮， 深度红移的荧光团。为了微调黄酸盐染料以在活体中有效成像， 系统，结构变化和相应的物理性质的调查是 必要通过Flav 7支架的系统衍生化，这项工作试图阐明 设计原则的发展，一个短波红外傅立叶共振能量转移（FRET）转- 在探测器上FRET探针对于成像是非常感兴趣的，因为它们可以导致更大的信号-时间比。 与游离染料相比的噪声比。我们的实验室旨在招募SWIR FRET对， 生物医学成像应用。使用先前的蛋白酶可切割接头，我们将 合成用于小组织肉瘤（STS）图像引导手术SWIRFRET探针。的 依赖于组织穿透SWIR光的FRET探针的开发将极大地改善临床应用。 诊断.