Near infrared thoracoscopy of tumoral protease activity for improved detection of peripheral lung cancer
Near infrared thoracoscopy of tumoral protease activity for improved detection of peripheral lung cancer
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DOI：
10.1002/ijc.21713
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发表时间：
2006-06-01
影响因子：
6.4
通讯作者：
Mahmood, U
中科院分区：
文献类型：
--
作者：
Figueiredo, JL;Alencar, H;Mahmood, U
使用“SMART”探头结合微导管荧光胸腔镜术在小鼠模型中评估了肿瘤检测的改进。这些成像探针在蛋白酶激活后荧光强度增加；组织蛋白酶B是本研究中使用的探针的主要激活剂。将Lewis肺癌细胞原位种植于胸膜下肺实质。静脉注射两种不同激发和发射波长的可激活近红外(NIR)探针，以确定波长是否会调制目标背景比(TBR)。对小鼠进行选择性插管和胸腔镜术。用0.8 mm外径成像导管同时记录白光(解剖)和近红外(NIR)图像。在两个被评估的波长对(680/700和750/780 nm激发/发射)下，未注射动物的肿瘤和正常肺之间的固有光度差异很小(p>；分别为0.3和p=0.4，TBR接近1)。在接受蛋白酶探针IV的小鼠中，肿瘤明显比邻近肺更具荧光(P<；0.0005为680/700，P<；0.006为750/780)，总有效率增加到约9倍。确认荧光显微镜和免疫组织化学相似，发现正常肺组织中组织蛋白酶B和荧光探针的表达水平非常低。总而言之，用近红外微导管成像的对组织蛋白酶B具有选择性的蛋白酶敏感的成像探针显著增加了TBR，使小的周围型肺肿瘤更容易被发现。在肺癌患者的分期或再分期中，这种方法可能是一种有用的辅助手段，以寻找胸膜和胸膜下间隙的微小病变。(C)2005年Wiley-Liss，Inc.
Improvement in tumor detection using "smart" probes in combination with microcatheter fluorescence thoracoscopy was evaluated in a mouse model. These imaging probes increase in fluorescence intensity after protease activation; cathepsin B is a major activator of the probes used in this study. Lewis lung carcinoma cells were orthotopically implanted in the subpleural lung parenchyma. Two activatable near infrared (NIR) probes with different excitation and emission wavelength were administered intravenously to determine whether wavelength would modulate target to background ratio (TBR). Mice were selectively intubated and thoracoscopy performed. A 0.8 mm outer diameter imaging catheter was used to record simultaneous white-light (anatomic) and NIR (protease expression) images. At both wavelength pairs evaluated (680/700 and 750/780 nm excitation/emission), the intrinsic luminosity differences between tumors and normal lung in uninjected animals was low (p > 0.3 and p = 0.4, respectively and TBR near 1). In mice receiving protease probes IV, tumors were significantly more fluorescent than adjacent lung (p < 0.0005 for 680/700 and p < 0.006 for 750/780) and TBR increased to approximately 9-fold. Confirmatory fluorescence microscopy and immunohistochemistry were similar and revealed that normal lung had very low levels when compared to tumors of cathepsin B and probe fluorescence. In conclusion, protease sensitive imaging probes selective for cathepsin B, imaged with NIR microcatheters, significantly increase the TBR, making small peripheral lung tumors more readily apparent. Such an approach may be a useful adjunct in staging or restaging patients with lung cancer to find minimal disease in the pleural and subpleural space. (c) 2005 Wiley-Liss, Inc.