Department of Pharmacology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Theranostics. 2020 Feb 10;10(7):3340-3350. doi: 10.7150/thno.41239. eCollection 2020.
Lymph node (LN) dissection followed by histological analysis is the current standard for diagnosis of LN metastasis but the method suffers from patient morbidity and low sensitivity of detection. Ultra-pH sensitive (UPS) nanoparticles show remarkable accuracy in the delineation of primary tumor margins for precision cancer surgery. Herein we investigate the effectiveness of UPS nanoparticles to detect cancer-involved LNs. : We synthesized a series of indocyanine green (ICG) conjugated UPS nanoparticles with distinct pK (UPS, UPS, and UPS). Systemically administered UPS-ICG nanoparticles in the 4T1.2-BALB/cj mouse model were imaged with real-time, near-infrared fluorescence (NIRF) to guide removal of LNs. imaging of gross tissue enabled quantification of fluorescence intensity. Histological analysis was used as the gold standard diagnostic test. : Macrophage uptake of UPS nanoparticles elevates the background signal in benign LNs. However, cancer foci within LNs show distinctive clustering of UPS-ICG fluorescence. UPS achieves accurate detection of metastatic LNs as shown by a receiver operating characteristic (ROC) area under the curve (AUC) of 0.96 ± 0.03. UPS and UPS offer decreased discriminatory power at ROC AUC of 0.73 ± 0.1 and 0.88 ± 0.07, respectively. : All UPS compositions show cancer-specific discrimination of metastatic LNs over benign LNs with the best outcomes from UPS. Detection of micro-metastatic LNs (cancer foci < 2 mm) remains a challenge. This study provides information on the detection of LN status for image-guided resection of metastatic LNs.
淋巴结 (LN) 解剖后进行组织学分析是目前诊断 LN 转移的标准方法，但该方法存在患者发病率高和检测灵敏度低的问题。超 pH 敏感 (UPS) 纳米颗粒在精确癌症手术中对原发性肿瘤边界的描绘具有显著的准确性。在此，我们研究了 UPS 纳米颗粒检测癌性 LN 的效果。我们合成了一系列具有不同 pK 值的吲哚菁绿 (ICG) 偶联 UPS 纳米颗粒（UPS、UPS 和 UPS）。将系统给予的 UPS-ICG 纳米颗粒在 4T1.2-BALB/cj 小鼠模型中进行实时近红外荧光 (NIRF) 成像，以指导 LN 的切除。对大体组织进行成像可定量荧光强度。组织学分析被用作金标准诊断测试。UPS 纳米颗粒被巨噬细胞摄取会增加良性 LN 的背景信号。然而，LN 内的癌灶显示出 UPS-ICG 荧光的独特聚集。UPS 通过 ROC 曲线下的面积（AUC）为 0.96±0.03 实现了转移性 LN 的准确检测。UPS 和 UPS 的 AUC 分别为 0.73±0.1 和 0.88±0.07，表明其鉴别能力降低。所有 UPS 成分均显示出转移性 LN 相对于良性 LN 的癌症特异性区分，其中 UPS 的结果最佳。对微转移性 LN（<2mm 的癌灶）的检测仍然是一个挑战。本研究提供了关于 LN 状态检测的信息，可用于指导转移性 LN 的切除。
