Prince Andrew C, Moore Lindsay S, Tipirneni Kiranya E, Ramesh Tushar, Limdi Mihir A, Bevans Stephanie L, Walsh Erika M, Greene Benjamin, Rosenthal Eben L, Warram Jason M
University of Alabama School of Medicine, Birmingham, AL, USA.
Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA.
Surg Oncol. 2018 Jun;27(2):225-230. doi: 10.1016/j.suronc.2018.04.004. Epub 2018 Apr 26.
Tumor proliferation often occurs from pathologic receptor upregulation. These receptors provide unique targets for near-infrared (NIR) probes that have fluorescence-guided surgery (FGS) applications. We demonstrate the use of three smart-targeted probes in a model of head and neck squamous cell carcinoma.
A dose escalation study was performed using IntegriSense750, ProSense750EX, and ProSense750FAST in mice (n = 5) bearing luciferase-positive SCC-1 flank xenograft tumors. Whole body fluorescence imaging was performed serially after intravenous injection using commercially available open-field (LUNA, Novadaq, Canada) and closed-field NIR systems (Pearl, LI-COR, Lincoln, NE). An ex vivo, whole-body biodistribution was conducted. Lastly, FGS was performed with IntegriSense750 to demonstrate orthotopic and metastatic disease localization.
Disease fluorescence delineation was assessed by tumor-to-background fluorescence ratios (TBR). Peak TBR values were 3.3 for 1 nmol ProSense750EX, 5.5 for 6 nmol ProSense750FAST, and 10.8 for 4 nmol IntegriSense750 at 5.5, 3, and 4 d post administration, respectively. Agent utility is unique: ProSense750FAST provides sufficient contrast quickly (TBR: 1.5, 3 h) while IntegriSense750 produces strong (TBR: 10.8) contrast with extended administration-to-resection time (96 h). IntegriSense750 correctly identified all diseased nodes in situ during exploratory surgeries. Ex vivo, whole-body biodistribution was assessed by tumor-to-tissue fluorescence ratios (TTR). Agents provided sufficient fluorescence contrast to discriminate disease from background, TTR>1. IntegriSense750 was most robust in neural tissue (TTR: 64) while ProSense750EX was superior localizing disease against lung tissue (TBR: 13).
All three agents appear effective for FGS.
肿瘤增殖常因病理受体上调而发生。这些受体为具有荧光引导手术（FGS）应用的近红外（NIR）探针提供了独特的靶点。我们展示了三种智能靶向探针在头颈部鳞状细胞癌模型中的应用。
对携带荧光素酶阳性SCC-1侧腹异种移植肿瘤的小鼠（n = 5）进行剂量递增研究，使用IntegriSense750、ProSense750EX和ProSense750FAST。静脉注射后，使用市售的开放视野（LUNA，加拿大诺瓦达科）和封闭视野近红外系统（Pearl，美国LI-COR，林肯，内布拉斯加州）连续进行全身荧光成像。进行了离体全身生物分布研究。最后，使用IntegriSense750进行FGS以显示原位和转移性疾病的定位。
通过肿瘤与背景荧光比率（TBR）评估疾病荧光描绘。给药后5.5、3和4天，1 nmol ProSense750EX的峰值TBR值为3.3，6 nmol ProSense750FAST为5.5，4 nmol IntegriSense750为10.8。各试剂的效用独特：ProSense750FAST能快速提供足够的对比度（TBR：1.5，3小时），而IntegriSense750在延长给药至切除时间（96小时）时产生强烈的对比度（TBR：10.8）。IntegriSense750在探索性手术期间正确识别了所有原位病变淋巴结。离体时，通过肿瘤与组织荧光比率（TTR）评估全身生物分布。各试剂提供了足够的荧光对比度以区分疾病与背景，TTR>1。IntegriSense750在神经组织中最稳定（TTR：64），而ProSense750EX在针对肺组织定位疾病方面更具优势（TBR：13）。
所有三种试剂似乎对FGS均有效。
