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使用弹性蛋白特异性分子探针可视化和定量前列腺癌中的细胞外基质

Visualization and Quantification of the Extracellular Matrix in Prostate Cancer Using an Elastin Specific Molecular Probe.

作者信息

Kader Avan, Brangsch Julia, Reimann Carolin, Kaufmann Jan O, Mangarova Dilyana B, Moeckel Jana, Adams Lisa C, Zhao Jing, Saatz Jessica, Traub Heike, Buchholz Rebecca, Karst Uwe, Hamm Bernd, Makowski Marcus R

机构信息

Department of Radiology, Institute of Integrative Neuroanatomy, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.

Department of Biology, Chemistry and Pharmacy, Institute of Biology, Freie Universität Berlin, Königin-Luise-Str. 1-3, 14195 Berlin, Germany.

出版信息

Biology (Basel). 2021 Nov 22;10(11):1217. doi: 10.3390/biology10111217.

Abstract

Human prostate cancer (PCa) is a type of malignancy and one of the most frequently diagnosed cancers in men. Elastin is an important component of the extracellular matrix and is involved in the structure and organization of prostate tissue. The present study examined prostate cancer in a xenograft mouse model using an elastin-specific molecular probe for magnetic resonance molecular imaging. Two different tumor sizes (500 mm and 1000 mm) were compared and analyzed by MRI in vivo and histologically and analytically ex vivo. The T1-weighted sequence was used in a clinical 3-T scanner to calculate the relative contrast enhancement before and after probe administration. Our results show that the use of an elastin-specific probe enables better discrimination between tumors and surrounding healthy tissue. Furthermore, specific binding of the probe to elastin fibers was confirmed by histological examination and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Smaller tumors showed significantly higher signal intensity ( > 0.001), which correlates with the higher proportion of elastin fibers in the histological evaluation than in larger tumors. A strong correlation was seen between relative enhancement (RE) and Elastica-van Gieson staining (R2 = 0.88). RE was related to inductively coupled plasma-mass spectrometry data for Gd and showed a correlation (R2 = 0.78). Thus, molecular MRI could become a novel quantitative tool for the early evaluation and detection of PCa.

摘要

人类前列腺癌(PCa)是一种恶性肿瘤,也是男性中最常被诊断出的癌症之一。弹性蛋白是细胞外基质的重要组成部分,参与前列腺组织的结构和组织。本研究使用弹性蛋白特异性分子探针进行磁共振分子成像,在异种移植小鼠模型中检测前列腺癌。通过体内MRI以及体外组织学和分析方法,对两种不同肿瘤大小(500立方毫米和1000立方毫米)进行了比较和分析。在临床3-T扫描仪中使用T1加权序列来计算探针给药前后的相对对比增强。我们的结果表明,使用弹性蛋白特异性探针能够更好地区分肿瘤与周围健康组织。此外,通过组织学检查以及激光烧蚀-电感耦合等离子体质谱法(LA-ICP-MS)证实了探针与弹性纤维的特异性结合。较小的肿瘤显示出明显更高的信号强度(>0.001),这与组织学评估中弹性纤维比例高于较大肿瘤相关。相对增强(RE)与弹性纤维-范吉森染色之间存在强相关性(R2 = 0.88)。RE与钆的电感耦合等离子体质谱数据相关,并显示出相关性(R2 = 0.78)。因此,分子MRI可能成为早期评估和检测前列腺癌的一种新型定量工具。

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