Advancing Fluorescence Imaging-guided Partial Nephrectomy with ClearICG

摘要 肾部分切除术正在成为肾癌越来越重要的治疗方法，因为更多的 超过60%的肾癌病例是在早期、局部阶段被诊断出来的。与根治性肾切除术相比， 肾部分切除术可以更好地保护肾功能，同时具有同等的肿瘤学效果 对于局限性肾癌的疗效，从而显著降低术后慢性肾脏的风险 疾病、肾衰竭和心血管事件。然而，肾肿瘤及其周围组织的准确可视化 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 在静脉注射吲哚青绿后，成像已被测试以确定肾脏肿瘤的边界 (ICG)，数百例临床病例表明，手术切缘阳性率并未因 ICG只能显示正常肾组织，不能选择性地积聚在肾癌细胞内。 与此同时，近40种新的荧光剂正在临床上接受荧光引导癌症的评估 手术中，只有2个能靶向和超荧光成像一个亚组的透明细胞肾细胞癌 (CcRCC)(约50%的病例)通过配体-受体相互作用，这两种新的探针未能靶向乳头 肾细胞癌是复发率较高的一种，其他类型的肾细胞癌。此外，该系统的复杂性 探头设计大大增加了制造成本，是ICG的100倍。的目标是 ClearNano Inc.将商业化一种安全、肾小管可清除、肿瘤靶向的近红外荧光剂，名为 “ClearICG”用于术中肾癌术中超荧光成像，包括ccRCC和pRCC。 该项目的成功将提高肾癌肾部分切除术的精确度，使肿瘤学 在总体医疗费用显著降低的情况下，肾功能结果可以同时得到改善 减少(约20%)。肾部分切除术将是ClearICG的进入市场，从长远来看，它比ICG更有优势 血液滞留和肿瘤靶向将使其在其他ICG辅助荧光引导下进一步取代ICG 需要重复注射和更高图像对比度的手术(扩大市场)。

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).