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.

项目摘要/摘要 生物医学成像是临床诊断中使用的一种基本方式。常见成像 诸如磁共振成像（MRI），X射线成像和正电子发射之类的方式 断层扫描（PET）受到成本，获取时间和/或使用电离辐射的限制。 荧光成像是生物医学成像的最佳方式，因为它是无创的， 便宜，安全的生活系统。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质区域。 优点，例如减少光散射和增加这些较低的组织渗透率 能量照片，与NIR相比，与Drives相比，相比之下会急剧增加 SWIR荧光团的创新。我们的小组最近开发了一个明亮的黄酮基swir 多胸染料名为Flav7。但是，增长的领域将受益于更明亮和 深红变荧光团。为了微调黄酮染料以有效成像 系统，结构变化的投资以及相应的光物理特性是 必要的。通过对FLAV7支架的系统衍生化，这项工作旨在阐明 swirfβrster共振能量转移（FRET）转向的设计原理 在探针上。 fret问题对于成像引起了极大的兴趣，因为它们可以导致更大的信噪 与游离染料相比，噪声比。我们的实验室旨在招募Swir Fret对以进行改进 生物医学成像应用。使用先例的蛋白酶可裂解的链接器，我们将 合成一个SWIR FRET探针，用于小型组织肉瘤（STS）的图像指导手术。 依赖于组织穿透swir光的FRET探针的开发将大大改善临床 诊断。