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

• 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
• 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

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).

摘要 肾部分切除术正成为肾癌越来越重要的治疗方法，因为更多的 超过60%的肾癌病例在早期、局部阶段被诊断出来。与根治性肾切除术相比， 肾部分切除术提供了更好的肾功能保护，同时具有相当的肿瘤学 对于局限性肾癌疗效显著，从而显著降低术后慢性肾功能衰竭的风险。 疾病、肾衰竭和心血管事件。然而，肾肿瘤的精确可视化及其 边界仍然是一个长期存在的技术挑战。虽然术中近红外（NIR）荧光 静脉注射吲哚菁绿色后，已测试成像以识别肾肿瘤边界 (ICG)，数百例临床病例表明，手术切缘阳性率并没有降低， ICG只能显示正常肾脏组织，不能选择性地在肾癌细胞中积累。 虽然近40种新的荧光剂正在临床上进行评估， 手术，其中只有2个可以靶向和高荧光成像的一个亚组的透明细胞肾细胞癌 （ccRCC）（约50%的所有病例）通过配体-受体相互作用，这两种新探针未能靶向乳头状癌。 RCC（pRCC），复发率较高的一种，以及其他类型的ccRCC。此外， 探针设计显著增加了制造成本，比ICG高出100倍以上。的目标 ClearNano Inc.是将一种安全的、可清除肾小管的、靶向肿瘤的近红外荧光剂商业化， “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部分切除术的精确性， 和肾功能的结果可以同时改善，而总的医疗费用显着 减少（约20%）。肾部分切除术将成为ClearICG的进入市场，从长远来看， 血液滞留和肿瘤靶向将使其能够进一步取代ICG在其他ICG辅助的荧光引导， 需要重复注射和更高图像对比度的手术（扩大市场）。