Image-Guided Surgery of Endocrine Glands and Their Tumors using Near-Infrared Flu

使用近红外流感图像引导内分泌腺及其肿瘤手术

基本信息

批准号：
8463526
负责人：
Hak Soo Choi
金额：
$ 46.16万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8463526
关键词：
Adhesions Adrenal Cortex Adrenal Glands Amines Anatomy Aniline Animal Model Applications Grants Aromatase Biodistribution Biomedical Engineering Blood Vessels Breast Carbon Catecholamines Cell membrane Cells Chemical Structure Chemicals Chemistry Clinic Clinical Clinical Trials Collaborations Color Contrast Media Data Development Dose Endocrine Endocrine Gland Neoplasms Endocrine Glands Estrone Excision Exhibits Family Family suidae Fascia Fluorescence Foundations Funding Future Gland Goals Grant Hormones Human Image Image-Guided Surgery Injection of therapeutic agent Iodine Kidney Laboratories Light Malignant neoplasm of lung Malignant neoplasm of ovary Manuscripts Mesentery Modeling Mus Nerve Operative Surgical Procedures Optics Ovary Pancreas Performance Pharmaceutical Preparations Plastic Surgical Procedures Preparation Production Property Quantitative Structure-Activity Relationship Rattus Relative (related person)Research Resected Sentinel Lymph Node Mapping Shapes Signal Transduction Simulate Specificity Sprague-Dawley Rats Steroids Structure Surgeon Surgical Oncologist System Testing Thyroid Gland Time Tissues Transgenic Mice Translating Tumor Tissue Universities Uterus Variant Vertebral column base chemical property cyanine cyanine dye falls flu fluorophore improved in vivo insulinoma intraoperative imaging intravenous injection malignant breast neoplasm novel optical imaging pharmacophore public health relevance research clinical testing scale up tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Endocrine tumors, such as insulinoma, are rare but notoriously difficult to treat surgically due to their small size and poor contrast using white light. Endocrine tumors, such as ovarian cancer, are common but equally difficult to treat surgically, with improved survival dependent on complete cytoreduction. Similarly, normal endocrine tissues, such as the thyroid gland and adrenal gland, can often be difficult to locate during surgery due to adhesions and overlying fascia. Our hypothesis is that near-infrared (NIR) fluorophores targeted to endocrine glands and their tumors will provide surgeons with sensitive, specific, and real-time image- guidance after a single, pre-operative, intravenous injection. When used with an appropriate intraoperative imaging system, NIR fluorescent light from 700 to 900 nm can provide surgeons with real-time localization of normal and diseased tissue, without changing the look of the surgical field. As part of a previously funded Bioengineering Research Partnership (BRP) grant, we have developed the FLARE" (Fluorescence-Assisted Resection and Exploration) image-guided surgery system. FLARE provides real-time imaging of surgical anatomy (i.e., color video) simultaneously with two independent channels of NIR fluorescent light (700 nm and 800 nm emission). One NIR channel is typically reserved for the tissue to be resected (e.g., tumor) while the other is reserved for tissue that needs to be avoided (e.g., nerves, blood vessels, normal glands, etc.). FLARE has already been translated to the clinic where it is being used in breast cancer sentinel lymph node (SLN) mapping, lung cancer SLN mapping, and plastic surgery. The resection of endocrine gland tumors (e.g., insulinoma and ovarian cancer) and the avoidance of normal endocrine tissue (e.g., thyroid and adrenal glands) represent a significant unmet clinical need, with no available contrast agents. In collaboration with the Henary/Strekowski/Patonay laboratory at Georgia State University, recognized leaders in the field of fluorophore chemistry, we have developed novel NIR fluorophores tailored to endocrine imaging (endocrine-specific NIR fluorophores; ESNFs). Sharing structural and chemical similarities with naturally occurring hormones and drugs, ESNFs provide high contrast for image-guided surgery after a single intravenous injection into mice, rats, and pigs. The specific aims of this grant are focused on the synthesis of three new chemical classes of ESNFs, scale-up from analytical to preparative production, and optimization of their optical and chemical properties. Completion of these aims will lay the foundation for future clinical testing of ESNFs during image-guided surgery.

描述（由申请人提供）：内分泌肿瘤（例如胰岛素瘤）很少见，但由于其体积小且白光对比度差而难以通过手术治疗。内分泌肿瘤，如卵巢癌，很常见，但同样难以通过手术治疗，生存率的提高依赖于完全细胞减灭术。同样，由于粘连和覆盖的筋膜，正常的内分泌组织（例如甲状腺和肾上腺）在手术过程中通常很难定位。我们的假设是，针对内分泌腺及其肿瘤的近红外（NIR）荧光团将在单次术前静脉注射后为外科医生提供敏感、特异性和实时的图像引导。当与适当的术中成像系统一起使用时，700 至 900 nm 的 NIR 荧光可以为外科医生提供正常组织和患病组织的实时定位，而无需改变手术区域的外观。作为先前资助的生物工程研究合作伙伴 (BRP) 拨款的一部分，我们开发了 FLARE”（荧光辅助切除和探索）图像引导手术系统。FLARE 同时提供手术解剖结构的实时成像（即彩色视频）具有两个独立的 NIR 荧光通道（700 nm 和 800 nm 发射），通常为要切除的组织保留一个 NIR 通道。 FLARE 已应用于临床，用于乳腺癌前哨淋巴结 (SLN)。）标测、肺癌前哨淋巴结标测和整形手术切除内分泌腺肿瘤（例如胰岛素瘤和卵巢癌）并避免正常内分泌组织（例如甲状腺和肾上腺）。由于没有可用的造影剂，我们与荧光团化学领域公认的领导者佐治亚州立大学 Henary/Strekowski/Patonay 实验室合作，开发了适合内分泌成像的新型近红外荧光团。内分泌特异性近红外荧光团； ESNF）。 ESNF 与天然激素和药物具有结构和化学相似性，在对小鼠、大鼠和猪进行单次静脉注射后，可为图像引导手术提供高对比度。这笔赠款的具体目标集中于合成三种新化学类别的 ESNF、从分析型生产扩大到制备型生产以及优化其光学和化学性质。这些目标的完成将为未来图像引导手术期间 ESNF 的临床测试奠定基础。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hydroxylated near-infrared BODIPY fluorophores as intracellular pH sensors.

羟基化近红外 BODIPY 荧光团作为细胞内 pH 传感器。

DOI：
发表时间：
2014-10-07
期刊：
影响因子：
0
作者：
Salim, Mohamed M;Owens, Eric A;Gao, Tielong;Lee, Jeong Heon;Hyun, Hoon;Choi, Hak Soo;Henary, Maged
通讯作者：
Henary, Maged

NIR fluorescent small molecules for intraoperative imaging.

用于术中成像的近红外荧光小分子。

DOI：
发表时间：
2015
期刊：
影响因子：
0
作者：
Owens, Eric A;Lee, Stephanie;Choi, JungMun;Henary, Maged;Choi, Hak Soo
通讯作者：
Choi, Hak Soo

Tailored near-infrared contrast agents for image guided surgery.

用于图像引导手术的定制近红外造影剂。

DOI：
发表时间：
2015-03-26
期刊：
影响因子：
7.3
作者：
Njiojob, Costyl N;Owens, Eric A;Narayana, Lakshminarayana;Hyun, Hoon;Choi, Hak Soo;Henary, Maged
通讯作者：
Henary, Maged

Near-Infrared Illumination of Native Tissues for Image-Guided Surgery.

用于图像引导手术的天然组织的近红外照明。

DOI：
发表时间：
2016-06-09
期刊：
影响因子：
7.3
作者：
Owens, Eric A;Hyun, Hoon;Dost, Tyler L;Lee, Jeong Heon;Park, GwangLi;Pham, Dang Huan;Park, Min Ho;Choi, Hak Soo;Henary, Maged
通讯作者：
Henary, Maged

Renal Clearable Organic Nanocarriers for Bioimaging and Drug Delivery.

用于生物成像和药物输送的肾脏可清除有机纳米载体。

DOI：
发表时间：
2016-10
期刊：
影响因子：
0
作者：
Kang, Homan;Gravier, Julien;Bao, Kai;Wada, Hideyuki;Lee, Jeong Heon;Baek, Yoonji;El Fakhri, Georges;Gioux, Sylvain;Rubin, Brian P;Coll, Jean;Choi, Hak Soo
通讯作者：
Choi, Hak Soo