Ultra-Low Background NIR Fluorophores for In Vivo Imaging and Image-Guided Surger

用于体内成像和图像引导手术的超低背景近红外荧光团

基本信息

  • 批准号:
    8112741
  • 负责人:
  • 金额:
    $ 68.14万
  • 依托单位:
  • 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 2014-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Near-infrared (NIR) fluorescence has the potential to revolutionize image-guided surgery. However, ideal fluorophores for in vivo, and eventually clinical, use have not yet been described. Under an NIH Bioengineering Research Partnership (BRP) grant, the PI's laboratory has developed a surgical imaging system that simultaneously, and in real-time, acquires two independent wavelengths of NIR fluorescence emission images along with color video images. The imaging system has already been translated to the clinic, and is being formally evaluated in three NIH-funded clinical trials. Nevertheless, the fundamental limitation to the future success of this technology is the development of NIR fluorophores that perform optimally in the body, and which can be made widely available to other academic researchers. To be clinically viable, the ideal NIR fluorophore requires certain optical properties, including excitation and emission H800 nm, and both a high extinction coefficient (5) and quantum yield (QY) in serum. However, the reason why existing NIR fluorophores perform so poorly in vivo has more to do with biodistribution and clearance. After IV injection, the ideal NIR fluorophore would rapidly equilibrate between the intravascular and extra vascular spaces and would be cleared efficiently via renal filtration. To date, every NIR fluorophore described in the literature suffers from two fundamental flaws: 1) hepatic clearance, which results in NIR fluorescence signal throughout the GI tract that persists for hours, and/or 2) non-specific background uptake in normal tissues, which typically persists for hours and results in a low signal-to-background ratio (SBR). This grant builds upon an observation we made two years ago using NIR fluorescent quantum dots (Choi et al., Nature Biotechnol. 2007; 25: 1165-70). Unexpectedly, and for reasons only partially understood, zwitterionic organic coatings resulted in extremely low non-specific tissue uptake, rapid renal clearance, and no serum protein binding. However, purely anionic or cationic coatings gave the opposite results. Based on these data, we began collaborating with Drs. Patonay and Strekowski at Georgia State University, leaders in the field of NIR fluorophore chemistry, to synthesize zwitterionic heptamethine indocyanine NIR fluorophores. The preliminary results, described herein, demonstrate that both non-targeted and tumor-targeted zwitterionic NIR fluorophores have remarkable optical and in vivo properties, including 800 nm fluorescence, high 5 and QY, rapid renal clearance, absence of protein binding, and ultra-low non-specific tissue uptake (i.e., background). The specific aims of this grant are focused on the synthesis of optimized zwitterionic NIR fluorophores for in vivo and surgical imaging, on validating their use as targeted diagnostic agents for prostate cancer, and for scale-up from analytical to preparative production. Completion of these aims will lay the foundation for future clinical testing during image-guided surgery. Importantly, we also present an intellectual property strategy that will permit free sharing of optimized NIR fluorophores within the academic community. PUBLIC HEALTH RELEVANCE: Near-infrared light is invisible to the human eye, but penetrates relatively deeply into living tissue. It is therefore ideal for image-guided surgery, because it provides surgeons with high- sensitivity, high-resolution detection of diseases, such as cancer, without changing the look of the surgical field. Although hardware systems that use near-infrared fluorescent light for image-guided surgery are already available, optimized fluorophores, or "light bulbs" are not. The goal of this grant is to develop a new class of ideal near-infrared fluorophores that can be injected into the bloodstream. These fluorophores would "stick" to tumors and other diseased tissue, but not to normal tissue.
描述(由申请人提供):近红外 (NIR) 荧光有可能彻底改变图像引导手术。然而,尚未描述用于体内和最终临床使用的理想荧光团。在 NIH 生物工程研究合作伙伴 (BRP) 的资助下,PI 的实验室开发了一种手术成像系统,该系统可以同时实时采集两个独立波长的近红外荧光发射图像以及彩色视频图像。该成像系统已经应用于临床,并正在 NIH 资助的三项临床试验中进行正式评估。然而,该技术未来成功的根本限制是近红外荧光团的开发,该荧光团在体内表现最佳,并且可以广泛供其他学术研究人员使用。 为了在临床上可行,理想的近红外荧光团需要一定的光学特性,包括激发和发射 H800 nm,以及血清中的高消光系数 (5) 和量子产率 (QY)。然而,现有近红外荧光团在体内表现如此差的原因更多地与生物分布和清除有关。静脉注射后,理想的近红外荧光团将在血管内和血管外空间之间快速平衡,并通过肾过滤有效清除。迄今为止,文献中描述的每种 NIR 荧光团都存在两个基本缺陷:1) 肝脏清除,导致 NIR 荧光信号在整个胃肠道中持续数小时,和/或 2) 正常组织中的非特异性背景摄取,通常持续数小时,导致信号背景比 (SBR) 较低。 这项资助建立在我们两年前使用近红外荧光量子点进行的观察的基础上(Choi 等人,Nature Biotechnol. 2007;25:1165-70)。出乎意料的是,由于仅部分了解的原因,两性离子有机涂层导致极低的非特异性组织摄取、快速的肾脏清除以及无血清蛋白结合。然而,纯阴离子或阳离子涂料给出了相反的结果。根据这些数据,我们开始与博士合作。佐治亚州立大学的 Patonay 和 Strekowski 是近红外荧光团化学领域的领导者,他们合成了两性离子七次甲基吲哚菁近红外荧光团。本文所述的初步结果表明,非靶向和肿瘤靶向两性离子 NIR 荧光团均具有显着的光学和体内特性,包括 800 nm 荧光、高 5 和 QY、快速肾脏清除、不存在蛋白质结合以及超低非特异性组织摄取(即背景)。 这笔资助的具体目标集中于合成用于体内和手术成像的优化两性离子近红外荧光团,验证其作为前列腺癌靶向诊断剂的用途,以及从分析型生产扩大到制备型生产。这些目标的完成将为未来图像引导手术中的临床测试奠定基础。重要的是,我们还提出了一项知识产权策略,允许在学术界免费共享优化的近红外荧光团。 公共健康相关性:近红外光人眼看不见,但能相对较深地渗透到活体组织中。因此,它非常适合图像引导手术,因为它为外科医生提供了对癌症等疾病的高灵敏度、高分辨率检测,而无需改变手术区域的外观。尽管使用近红外荧光进行图像引导手术的硬件系统已经可用,但优化的荧光团或“灯泡”还没有。这笔赠款的目标是开发一类可以注射到血液中的新型理想近红外荧光团。这些荧光团会“粘附”在肿瘤和其他患病组织上,但不会粘附在正常组织上。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Hak Soo Choi其他文献

Hak Soo Choi的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Hak Soo Choi', 18)}}的其他基金

Long-Acting, Short-Residing Nanochelators for Iron Overload Therapy
用于铁过载治疗的长效、短效纳米螯合剂
  • 批准号:
    10585319
  • 财政年份:
    2023
  • 资助金额:
    $ 68.14万
  • 项目类别:
Nanochelation Therapies for Iron Overload Disorders
纳米螯合疗法治疗铁过载疾病
  • 批准号:
    10318332
  • 财政年份:
    2021
  • 资助金额:
    $ 68.14万
  • 项目类别:
Nanochelation Therapies for Iron Overload Disorders
纳米螯合疗法治疗铁过载疾病
  • 批准号:
    10437625
  • 财政年份:
    2021
  • 资助金额:
    $ 68.14万
  • 项目类别:
Image-Guided Drug Delivery and Treatment for GIST
图像引导胃肠道间质瘤的药物输送和治疗
  • 批准号:
    9792375
  • 财政年份:
    2018
  • 资助金额:
    $ 68.14万
  • 项目类别:
Image-Guided Drug Delivery for Pancreatic Neuroendocrine Tumor.
图像引导胰腺神经内分泌肿瘤的药物输送。
  • 批准号:
    9302133
  • 财政年份:
    2017
  • 资助金额:
    $ 68.14万
  • 项目类别:
Image-Guided Drug Delivery for Pancreatic Neuroendocrine Tumor
图像引导胰腺神经内分泌肿瘤给药
  • 批准号:
    10167387
  • 财政年份:
    2017
  • 资助金额:
    $ 68.14万
  • 项目类别:
Image-Guided Drug Delivery for Pancreatic Neuroendocrine Tumor.
图像引导胰腺神经内分泌肿瘤的药物输送。
  • 批准号:
    9566182
  • 财政年份:
    2017
  • 资助金额:
    $ 68.14万
  • 项目类别:
Ultra-Low Background NIR Fluorophores for In Vivo Imaging and Image-Guided Surger
用于体内成像和图像引导手术的超低背景近红外荧光团
  • 批准号:
    8514598
  • 财政年份:
    2010
  • 资助金额:
    $ 68.14万
  • 项目类别:
Ultra-Low Background NIR Fluorophores for In Vivo Imaging and Image-Guided Surger
用于体内成像和图像引导手术的超低背景近红外荧光团
  • 批准号:
    7937599
  • 财政年份:
    2010
  • 资助金额:
    $ 68.14万
  • 项目类别:
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
  • 批准号:
    8117244
  • 财政年份:
    2010
  • 资助金额:
    $ 68.14万
  • 项目类别:

相似海外基金

More sustainable biocatalytic imine reductions to chiral amines with hydrogen-driven NADPH recycling operated in batch and continuous flow
通过批量和连续流操作的氢驱动 NADPH 回收,更可持续地生物催化亚胺还原为手性胺
  • 批准号:
    2889869
  • 财政年份:
    2023
  • 资助金额:
    $ 68.14万
  • 项目类别:
    Studentship
Organoborane-catalysed approaches to biologically active amines
有机硼烷催化制备生物活性胺的方法
  • 批准号:
    EP/Y00146X/1
  • 财政年份:
    2023
  • 资助金额:
    $ 68.14万
  • 项目类别:
    Research Grant
Transforming Amines into Complex Polycyclic Molecules and Bioactive Natural Products
将胺转化为复杂的多环分子和生物活性天然产物
  • 批准号:
    2247651
  • 财政年份:
    2023
  • 资助金额:
    $ 68.14万
  • 项目类别:
    Standard Grant
Ti-catalyzed cascading hydroaminoalkylation as a route to complex functionalized amines
Ti 催化级联氢氨基烷基化作为制备复杂官能化胺的途径
  • 批准号:
    10750347
  • 财政年份:
    2023
  • 资助金额:
    $ 68.14万
  • 项目类别:
New Photocatalytic C-C Bond-Forming Reactivity of Unprotected Primary Amines
未受保护伯胺的新光催化 C-C 键形成反应
  • 批准号:
    EP/X026566/1
  • 财政年份:
    2023
  • 资助金额:
    $ 68.14万
  • 项目类别:
    Research Grant
Nickel Cross-Coupling Cascades with α-Heteroatom Radicals to Prepare Sterically Hindered Alcohols and Amines
镍与α-杂原子自由基交叉偶联级联制备位阻醇和胺
  • 批准号:
    10604535
  • 财政年份:
    2023
  • 资助金额:
    $ 68.14万
  • 项目类别:
Mining the air for amines
开采空气中的胺
  • 批准号:
    2752688
  • 财政年份:
    2022
  • 资助金额:
    $ 68.14万
  • 项目类别:
    Studentship
Towards a better understanding of the effect of the pentafluorosulfanyl group on the lipophilicity and acid/base properties of alcohols and amines
更好地了解五氟硫基对醇和胺的亲脂性和酸/碱性质的影响
  • 批准号:
    571856-2021
  • 财政年份:
    2022
  • 资助金额:
    $ 68.14万
  • 项目类别:
    Alliance Grants
Development of Strategies for the Enantioselective Synthesis of Heterocycles and Acyclic Amines
杂环和无环胺对映选择性合成策略的发展
  • 批准号:
    10656344
  • 财政年份:
    2022
  • 资助金额:
    $ 68.14万
  • 项目类别:
Pd-Catalyzed C(sp3)-H Functionalizations Directed by Free Alcohols and Boc-Protected Amines
由游离醇和 Boc 保护的胺引导的 Pd 催化 C(sp3)-H 官能化
  • 批准号:
    10606508
  • 财政年份:
    2022
  • 资助金额:
    $ 68.14万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了