Advancing Fluorescence Imaging-guided Partial Nephrectomy with ClearICG

利用 ClearICG 推进荧光成像引导的部分肾切除术

基本信息

批准号：
10379857
负责人：
Mengxiao Yu
金额：
$ 38.53万
依托单位：
CLEARNANO, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-23 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10379857
关键词：
ABCB1 gene Advanced Development Area Under Curve Artificial nanoparticles Biodistribution Blood Blood Circulation Cancerous Canis familiaris Cardiovascular system Cells Chronic Kidney Failure Clear Cell Clear cell renal cell carcinoma Clinic Clinical Clinical Trials Diagnosis Dose Drug Kinetics Enzymes Evaluation Event Excision Fluorescence Fluorescent Dyes Goals Half-Life Human In Vitro Indocyanine Green Injections Investigational Drugs Kidney Kidney Failure Kidney Neoplasms Life Ligands Mediating Medical Molecular Weight Names Nanotechnology Nature Near-infrared optical imaging Nephrectomy Normal Cell Papillary Patients Peptides Pharmaceutical Preparations Pharmacology and Toxicology Phase Polyethylene Glycols Postoperative Period Production Quality of life ROC Curve Reaction Recurrence Regulatory Pathway Renal carcinoma Renal function Renal tubule structure Risk Small Business Innovation Research Grant Sprague-Dawley Rats Subgroup Surgeon Surgical margins Techniques Testing Time Tissues Toxicology Translating Tubular formation Visualization acute toxicity base biomaterial compatibility cancer cell cancer surgery clinically relevant contrast imaging cost cyanine dye design fluorescence imaging fluorescence-guided surgery fluorophore functional outcomes good laboratory practice image guided imaging agent imaging system improved in vivo innovation intravenous injection mouse model nanomedicine nanoparticle nanosized overexpression patient derived xenograft model preservation quality assurance receptor receptor expression success tumor

项目摘要

Abstract Partial nephrectomy is becoming an increasingly important treatment for kidney cancer because more than 60% of kidney cancer cases are diagnosed in early, localized stages. Compared to radical nephrectomy, partial nephrectomy offers much better preservation of renal function while having an equivalent oncological efficacy for the localized kidney cancer, thereby significantly reducing the postoperative risk of chronic kidney disease, kidney failure and cardiovascular events. However, accurate visualization of renal tumor and its boundary remains a long-standing technique challenge. Although intraoperative near-infrared (NIR) fluorescence imaging has been tested to identify the renal tumor boundary after intravenous injection of indocyanine green (ICG), hundreds of clinical cases show that the rate of positive surgical margin has not been reduced because ICG can only visualize the normal kidney tissues and is not able to selectively accumulate in kidney cancer cells. While nearly 40 new fluorescent agents are being evaluated in the clinics for fluorescence-guided cancer surgery, only 2 of them can target and hyper-fluorescently image a subgroup of clear cell renal cell carcinoma (ccRCC) (~50% of all cases) through ligand-receptor interactions and these two new probes fail to target papillary RCC (pRCC), the one with higher recurrence rate, and other types of ccRCC. In addition, the complexity in the probe design significantly increases the manufacture cost, >100 times higher than that of ICG. The goal of ClearNano Inc. is to commercialize a safe, renal-tubule-clearable, tumor targeting NIR fluorescent agent, named “ClearICG” for intraoperative, hyper-fluorescence imaging of kidney cancer including both ccRCC and pRCC. The success of this project will advance the precision of partial nephrectomy for kidney cancer so that oncological and renal functional outcomes can be simultaneously improved while overall medical expense is significantly reduced (~20%). Partial nephrectomy will be the entry market for ClearICG, and its merits over ICG in the long blood retention and tumor targeting will allow it to further replace ICG in other ICG-assisted fluorescence-guided surgeries that require repeated injections and higher image contrast (expanded market).

抽象的肾部分切除术正成为肾癌越来越重要的治疗方法，因为更多与根治性肾切除术相比，超过 60% 的肾癌病例是在早期、局部阶段被诊断出来的。肾部分切除术可以更好地保留肾功能，同时具有同等的肿瘤学效果对局限性肾癌有效，从而显着降低术后慢性肾病风险然而，肾肿瘤及其疾病的准确可视化。尽管术中近红外（NIR）荧光检测边界仍然是一个长期存在的技术挑战。静脉注射吲哚菁绿后，成像已测试可识别肾肿瘤边界（ICG），数百个临床病例表明，手术切缘阳性率并没有降低，因为 ICG只能观察正常肾组织，不能选择性地在肾癌细胞中积累。近 40 种新型荧光剂正在临床中针对荧光引导癌症进行评估手术中，只有 2 个可以针对透明细胞肾细胞癌的一个亚组进行靶向和高荧光成像 (ccRCC)（约占所有病例的 50%）通过配体-受体相互作用，这两种新探针未能靶向乳头状 RCC（pRCC）是复发率较高的一种，与其他类型的 ccRCC 相比，其复杂性也更高。探针设计显着增加了制造成本，比ICG的目标高出>100倍。 ClearNano Inc. 将商业化一种安全的、肾小管可清除的、肿瘤靶向 NIR 荧光剂，名为 “ClearICG”用于肾癌（包括 ccRCC 和 pRCC）的术中超荧光成像。该项目的成功将提高肾癌肾部分切除术的精准度，从而使肿瘤学可以同时改善肾功能结果，同时显着降低总体医疗费用减少（~20%），部分肾切除术将成为 ClearICG 的进入市场，从长远来看，它比 ICG 更有优势。血液保留和肿瘤靶向将使其在其他ICG辅助荧光引导中进一步取代ICG 需要重复注射和更高图像对比度的手术（扩大的市场）。