Biocompatible fluorophores for shortwave infrared imaging

用于短波红外成像的生物相容性荧光团

• 批准号: 10737471
• 负责人: Ellen May Sletten
• 金额: $ 38.21万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-13 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737471
• 关键词: Animal Model; Animals; Basic Science; Biological; Biological Process; Biology; Biopsy; Cells; Clinical; Collaborations; Color; Contrast Media; Custom; Detection; Development; Disease; Electromagnetics; Engineering; Environment; Excision; Formulation; Foundations; Free Energy; Gel; Goals; Grant; Human; Image; Imaging Techniques; Injections; Integrins; Label; Laboratories; Lasers; Lead; Learning; Light; Lymph; Lymph Node Mapping; Lymphatic System; Malignant Neoplasms; Mammals; Measures; Metastatic Neoplasm to Lymph Nodes; Methods; Micelles; Modification; Molecular; Mus; Neoplasm Metastasis; Noise; Operative Surgical Procedures; Organic Chemistry; Organism; Penetration; Performance; Periodicity; Polymers; Property; Reporting; Resolution; Sentinel; Sentinel Lymph Node Mapping; Sepharose; Short Waves; Shortwave Infrared Imaging; Signal Transduction; Site; Skin; System; Tail; Testing; Time; Tissues; Toxic effect; Variant; Visualization; Water; Work; absorption; arm; biomaterial compatibility; cancer imaging; chromophore; clinical application; clinical diagnostics; clinically relevant; copolymer; experimental group; experimental study; fluorophore; human disease; human model; improved; in vivo; light scattering; lymph nodes; lymphatic drainage; lymphatic imaging; millimeter; multiplexed imaging; optical imaging; real-time images; scaffold; small molecule; theories; tumor

The shortwave infrared (SWIR) region of the electromagnetic spectrum has become an exciting avenue for imaging in mammals due to the increased penetration of light through tissue, decreased light scattering, and minimal autofluorescence. In the previous granting period, we showcased an additional advantage of the SWIR region– the enhanced spectral real estate which facilitates non-invasive multicolor imaging in mice. Taken together, all these advantages set the stage for: 1) fundamental biological studies in animal models analogous to those which have been enormously successful in cells and transparent organisms, 2) the ability to evaluate controls in same animal as the experimental group, and 3) advanced clinical diagnostics for both intraoperative and non-invasive use. While the SWIR region has great potential, it cannot be realized without biocompatible contrast agents. This proposal focuses on contrast agent development for high resolution multicolor imaging in the SWIR region, building on the expertise we have gained in polymethine fluorophores over the last granting period. We have prepared over 100 polymethine fluorophores and gained predictive metrics on the most classical photophysical parameters of lmax.abs, lmax,em and FF. We have also learned some key lessons regarding utility of the fluorophores including how to solubilize them in water and have gained appreciation for the different approaches to formulating fluorophores for imaging. In collaboration with the Bruns laboratory, we demonstrated excitation-based multicolor imaging with fluorophores well-matched to common laser lines. In the next granting period, we specifically focus on optimizing fluorophores for use in excitation-based multiplexing with detection in the high-resolution region of the SWIR (above 1400 nm) such that mm resolution can be achieved. Aim 1 explores the chromophore scaffold itself optimizing the photophysical properties for maximum absorption at commercial laser lines and emission >1400 nm. We take a physical organic chemistry approach to fluorophore optimization and capitalize on the continually growing, fully characterized set of systematically modified fluorophores our laboratory has prepared. Our work is aided by computation and theory collaborations with the Lopez and Caram Laboratories. Aim 2 transforms the lead fluorophores from aim 1 into water-soluble, targeted contrast agents. Finally in Aim 3, we aim image the lymphatic system, demonstrating the need for mm resolution imaging and then using excitation-based multicolor imaging to evaluate sentinel lymph node mapping and cancer metastasis.

电磁光谱的短波红外(SWIR)区域已经成为一种令人兴奋的途径 哺乳动物的成像是由于光对组织的穿透增加，光散射减少，以及 最小的自发荧光。在之前的授权期内，我们展示了SWIR的另一个优势 区域-增强的光谱区域，便于在小鼠身上进行非侵入性多色成像。已被占用 总而言之，所有这些优势为：1)在类似的动物模型中进行基础生物学研究奠定了基础 对于那些在细胞和透明生物体中取得巨大成功的人，2)评估 与试验组动物相同的对照组，以及3)术中两种疾病的先进临床诊断 和非侵入性使用。 虽然SWIR区域具有巨大的潜力，但如果没有生物兼容的造影剂，它是无法实现的。这 提案的重点是开发用于SWIR区域高分辨率多色成像的造影剂， 基于我们在上一次授权期内在多甲基荧光团方面获得的专业知识。我们有 制备了100多个多甲基荧光团，并获得了对最经典光物理的预测度量 Lmax，abs，lmax，em，ff的参数。我们还学到了一些关于荧光团用途的重要经验。 包括如何将它们溶解在水中，并对不同的配方方法获得了赞赏 用于成像的荧光团。在与布朗斯实验室的合作中，我们展示了基于激发的多彩 使用荧光团进行成像，与普通激光线路匹配良好。 在接下来的授权期内，我们将重点放在优化荧光团以用于基于激发的 在SWIR的高分辨率区域(高于1400 nm)中进行多路传输和检测，使得mm分辨率 是可以实现的。目标1探索发色团支架本身，优化其光物理性能 商用激光谱线的最大吸收和发射&gt；1400 nm。我们学了一门物理有机化学 优化荧光团的方法，并利用不断增长的、完全特征化的 我们实验室制备了系统修饰的荧光团。我们的工作得到了计算和理论的帮助。 与洛佩兹和卡拉姆实验室的合作。目标2将铅荧光团从目标1转化为 水溶性靶向造影剂。最后，在目标3中，我们对淋巴系统进行成像，演示 需要毫米分辨率成像，然后使用基于激发的多色成像来评估哨兵淋巴 结节标测和癌症转移。

项目成果

Shortwave infrared polymethine fluorophores matched to excitation lasers enable non-invasive, multicolour in vivo imaging in real time.

与激发激光器相匹配的短波红外多胸荧光团可实时实时非侵入性，多色在体内成像。

• DOI: 10.1038/s41557-020-00554-5
• 发表时间: 2020-12
• 期刊: Nature chemistry
• 影响因子: 21.8
• 作者: Cosco ED;Spearman AL;Ramakrishnan S;Lingg JGP;Saccomano M;Pengshung M;Arús BA;Wong KCY;Glasl S;Ntziachristos V;Warmer M;McLaughlin RR;Bruns OT;Sletten EM
• 通讯作者: Sletten EM

Water-soluble chromenylium dyes for shortwave infrared imaging in mice.

• DOI: 10.1016/j.chempr.2023.08.021
• 发表时间: 2023-09
• 期刊: Chem
• 影响因子: 23.5
• 作者: Shang Jia;Eric Y Lin;Emily B. Mobley;Irene Lim;Lei Guo;Shivakrishna Kallepu;Philip S. Low;Ellen M. Sletten

Counterion Pairing Effects on a Flavylium Heptamethine Dye.

• DOI: 10.1111/php.13531
• 发表时间: 2022-03
• 期刊: Photochemistry and photobiology
• 影响因子: 3.3
• 作者: Pengshung M;Cosco ED;Zhang Z;Sletten EM
• 通讯作者: Sletten EM

Bright Chromenylium Polymethine Dyes Enable Fast, Four-Color In Vivo Imaging with Shortwave Infrared Detection.

• DOI: 10.1021/jacs.0c11599
• 发表时间: 2021-05-12
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Cosco ED;Arús BA;Spearman AL;Atallah TL;Lim I;Leland OS;Caram JR;Bischof TS;Bruns OT;Sletten EM
• 通讯作者: Sletten EM

Extending optical chemical tools and technologies to mice by shifting to the shortwave infrared region.

• DOI: 10.1016/j.cbpa.2022.102131
• 发表时间: 2022-06
• 期刊: Current opinion in chemical biology
• 影响因子: 7.8