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.

项目概要/摘要 生物医学成像是临床诊断中常用的重要方式。 磁共振成像 (MRI)、X 射线成像和正电子发射等模式 断层扫描 (PET) 受到成本、采集时间和/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， 目前，荧光成像使用近红外光。 （NIR，700–1000 nm），但短波红外区域（SWIR，1000–2000 nm） 电磁频谱已成为荧光成像的优越区域。 这些较低的优点包括减少光散射和增加组织穿透性 能量光子，与 NIR 相比导致对比度急剧增加并驱动 我们的团队最近开发了一种明亮的基于 Flavylium 的 SWIR。 名为 Flav7 的聚次甲基染料然而，更明亮和更明亮的领域将受益。 深度红移荧光团，以微调黄鎓染料以实现有效的活体成像。 系统，结构变化和相应光物理性质的研究 通过对 Flav7 支架进行系统衍生，这项工作旨在阐明这一点。 开发 SWIR Fărster 共振能量转移 (FRET) 转动的设计原则 FRET 探针对成像非常感兴趣，因为它们可以产生更大的信号到- 我们的实验室旨在招募 SWIR FRET 对以改进噪声比。 使用先例的蛋白酶可切割接头，我们将 合成用于小组​​织肉瘤（STS）图像引导手术的 SWIR FRET 探针。 开发依赖于组织穿透 SWIR 光的 FRET 探针将极大地改善临床 诊断。