Colonic adenocarcinomas: Near-infrared microcatheter imaging of smart probes for early detection - Study in mice

Colonic adenocarcinomas: Near-infrared microcatheter imaging of smart probes for early detection - Study in mice
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DOI:
10.1148/radiol.2441052114
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发表时间:
2007-07-01
期刊:
影响因子:
19.7
通讯作者:
Mahmood, Umar
Mahmood, Umar
中科院分区:
医学1区
文献类型:
--
作者:
Alencar, Herlen;Funovics, Martin A.;Mahmood, Umar

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目的:为了前瞻性地评估微光纤导管,同时记录白色光和近红外(NIR)图像,以揭示结肠肿瘤后,静脉注射可激活的“智能”探针,增加在近红外荧光蛋白酶activation.Materials和方法:机构动物护理委员会批准所有动物实验。将CT 26肿瘤细胞原位植入C57 BL 6/ J小鼠的降结肠中(n = 10)。13天后,小鼠静脉内接受2 nmol的蛋白酶敏感探针,其具有组织蛋白酶B作为主要激活剂(n = 5)或盐水(对照动物[ n = 5])。一天后,使用微导管成像对动物进行无创检查,直至脾曲。切除的结肠随后进行评价,荧光成像,组织学检查,组织蛋白酶B免疫组化。使用Student t检验进行统计分析,P <0.05被认为表明存在显着差异。结果:光纤成像的结果表明,所有肿瘤都可以用蛋白酶可激活探针看到,即使它们在白色光成像中不太明显。探针给药后,NIR通道中肿瘤与邻近正常粘膜的靶-背景比(TBR)为8.86(P = 0.001),而基于亮度的白色光图像的TBR为1.14(P > 0.5)。肿瘤NIR荧光强度在探针注射的动物中比在对照动物中大30倍以上,表明在病变中记录的基本上所有信号都来自可活化探针施用。免疫组化结果证实组织蛋白酶B过表达的肿瘤相比,邻近mucosal.Conclusion:近红外成像微导管结合蛋白酶激活的智能探针的使用结果在一个信标效应,突出肿瘤高TBRs,因此,这项技术可能是一个潜在的有用的辅助白色光结肠镜检查在未来。(c)RSNA,2007年。
Purpose: To prospectively evaluate the ability of micro-fiberoptic catheters, which simultaneously record white light and near-infrared (NIR) images, to reveal colonic neoplasms after the intravenous administration of activatable " smart" probes that increase in NIR fluorescence subsequent to protease activation.Materials and Methods: The institutional animal care committee approved all animal experiments. CT26 tumor cells were orthotopically implanted into the descending colon of C57BL6/ J mice (n = 10). Thirteen days later, mice intravenously received either 2 nmol of a protease-sensing probe that had cathepsin B as a major activator (n = 5) or saline (control animals [ n = 5]). One day later, animals were noninvasively examined to the point of the splenic flexure by using microcatheter imaging. Excised colons were subsequently evaluated with epifluorescence imaging, histologic examination, and cathepsin B immunohistochemistry. Student t test was used for statistical analysis, with P < .05 considered to indicate a significant difference.Results: Results with fiberoptic imaging demonstrated that all tumors were visible with the protease- activatable probe, even when they were not readily apparent at white light imaging. A target-to-background ratio (TBR) of 8.86 for tumor to adjacent normal mucosa was achieved in the NIR channel after probe administration ( P = .001), whereas white light images resulted in a TBR of 1.14 ( P > .5) based on luminosity. The tumoral NIR fluorescence intensity was more than 30-fold greater in probe- injected animals than in control animals, indicating that essentially all of the signal recorded in lesions was from activatable probe administration. Results of immunohistochemistry confirmed cathepsin B overexpression in the tumor compared with adjacent mucosa.Conclusion: The use of NIR imaging microcatheters combined with protease-activatable smart probes results in a beacon effect that highlights tumors with high TBRs; this technique thus may be a potentially useful adjunct to white light colonoscopy in the future. (c) RSNA, 2007.