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Rapid and Accurate Visualization of Breast Tumors with a Fluorescent Probe Targeting α-Mannosidase 2C1
ACS Central Science ( IF 18.2 ) Pub Date : 2020-10-29 , DOI: 10.1021/acscentsci.0c01189
Kyohhei Fujita , Mako Kamiya 1 , Takafusa Yoshioka , Akira Ogasawara , Rumi Hino 2 , Ryosuke Kojima 1 , Hiroaki Ueo 3 , Yasuteru Urano 4
Affiliation  

Accurate detection of breast tumors and discrimination of tumor from normal tissues during breast-conserving surgery are essential to reduce the risk of misdiagnosis or recurrence. However, existing probes show substantial background signals in normal breast tissues. In this study, we focus on glycosidase activities in breast tumors. We synthesized a series of 12 fluorescent probes and performed imaging-based evaluation on surgically resected human breast specimens. Among them, the α-mannosidase-reactive fluorescent probe HMRef-αMan detected breast cancer with 90% sensitivity and 100% specificity. We identified α-mannosidase 2C1 as the target enzyme and confirmed its overexpression in various breast tumors. We found that fibroadenoma, the most common benign breast lesion in young woman, tends to have higher α-mannosidase 2C1 activity than malignant cancer. Combined application of green-emitting HMRef-αMan and a red-emitting γ-glutamyltranspeptidase probe enabled efficient dual-color, dual-target optical discrimination of malignant and benign tumors.

中文翻译:

用靶向α-甘露糖苷酶2C1的荧光探针快速准确地观察乳腺肿瘤

在保乳手术中准确检测乳腺肿瘤和区分正常组织对减少误诊或复发的风险至关重要。然而,现有的探针在正常的乳腺组织中显示出实质性的背景信号。在这项研究中,我们专注于乳腺肿瘤中的糖苷酶活性。我们合成了一系列的12种荧光探针,并对通过手术切除的人类乳房标本进行了基于成像的评估。其中,α-甘露糖苷酶反应性荧光探针HMRef-αMan以90%的敏感性和100%的特异性检测出乳腺癌。我们确定α-甘露糖苷酶2C1为目标酶,并证实其在多种乳腺肿瘤中的过度表达。我们发现纤维腺瘤是年轻女性中最常见的良性乳腺病变,趋于具有比恶性癌症更高的α-甘露糖苷酶2C1活性。结合使用绿色发光的HMRef-αMan和红色发光的γ-谷氨酰转肽酶探针,可以对恶性和良性肿瘤进行有效的双色,双靶光学鉴别。
更新日期:2020-12-23
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