Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Ann Surg Oncol. 2010 Apr;17(4):1094-100. doi: 10.1245/s10434-009-0868-8. Epub 2009 Dec 22.
Neuroendocrine tumors of the pancreas, such as insulinoma, are difficult to localize, and complete resection is essential for cure. Our hypothesis is that a near-infrared (NIR) fluorophore exhibiting uptake in insulinoma could provide high-sensitivity detection intraoperatively.
The optical properties of methylene blue (MB) were measured in vitro in 100% serum at 37 degrees C and in vivo after tissue uptake. MB was injected as a rapid intravenous bolus at doses ranging from 0.25 to 2 mg/kg into wildtype rats and pigs, and into insulinoma-bearing transgenic mice. The FLARE imaging system was used to acquire color video and NIR fluorescence images simultaneously and in real-time. The signal-to-background ratios (SBR) of tissues and tumors were quantified using FLARE software.
When appropriately diluted, MB exhibits moderate NIR fluorescence emission peaking at 688 nm. At doses > or =1 mg/kg, certain normal tissues, such as pancreas, accumulate MB and remain NIR fluorescent for up to 1 h with an SBR > or = 1.6. MB spectral properties are maintained after uptake into tissue. Interestingly, insulinoma exhibits even higher MB signal than normal pancreas, resulting in insulinoma-to-pancreas ratios of 3.7 and insulinoma-to-muscle ratios of 16.2. MB permitted high-sensitivity, real-time localization of primary, multicentric, and metastatic insulinoma and permitted differentiation among tumor, normal pancreas, and other abdominal structures.
A single intravenous injection of a clinically available, commonly used NIR fluorophore provides prolonged intraoperative localization of normal pancreas and insulinoma using invisible NIR fluorescent light.
胰腺神经内分泌肿瘤，如胰岛素瘤，难以定位，彻底切除是治愈的关键。我们的假设是，一种在胰岛素瘤中摄取的近红外（NIR）荧光团可以在术中提供高灵敏度的检测。
在 37°C 的 100%血清中测量了亚甲蓝（MB）的光学特性，并在组织摄取后进行了体内测量。MB 以 0.25 至 2mg/kg 的剂量快速静脉推注到野生型大鼠和猪体内，并注射到胰岛素瘤转基因小鼠体内。使用 FLARE 成像系统同时实时采集彩色视频和 NIR 荧光图像。使用 FLARE 软件定量组织和肿瘤的信号背景比（SBR）。
当适当稀释时，MB 表现出适度的 NIR 荧光发射，峰值在 688nm。在剂量≥1mg/kg 时，某些正常组织，如胰腺，会积累 MB，并保持 NIR 荧光长达 1 小时，SBR≥1.6。MB 的光谱特性在被组织摄取后得以保持。有趣的是，胰岛素瘤表现出比正常胰腺更高的 MB 信号，导致胰岛素瘤与胰腺的比值为 3.7，胰岛素瘤与肌肉的比值为 16.2。MB 允许高灵敏度、实时定位原发性、多中心和转移性胰岛素瘤，并允许区分肿瘤、正常胰腺和其他腹部结构。
单次静脉注射一种临床可用的、常用的 NIR 荧光团，使用不可见的 NIR 荧光，可长时间定位正常胰腺和胰岛素瘤。
