松弛的纤维粘连蛋白:子宫内膜异位症病变成像的潜在新靶点。

IF 3.1 3区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Belinda Trachsel, Stefan Imobersteg, Giulia Valpreda, Gad Singer, Regula Grabherr, Mark Ormos, Irene A Burger, Rahel A Kubik-Huch, Roger Schibli, Viola Vogel, Martin Béhé
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引用次数: 0

摘要

背景:子宫内膜异位症的特点是子宫内膜组织异位。虽然子宫内膜异位症被认为是良性的,但其病变具有类似肿瘤的特性,如组织侵袭和细胞外基质重塑。子宫内膜异位症的一个主要临床障碍是诊断。超声波和核磁共振成像等诊断方法往往无法检测出所有病变,而影像学检查和临床症状之间是否存在明确的相关性仍存在争议。因此,我们的目标是找到一个潜在的靶点,对活跃的子宫内膜异位病灶进行成像:在研究中,我们采用了临床前放射性示踪剂[111In]In-FnBPA5,它能与松弛的纤维粘连蛋白特异性结合--纤维粘连蛋白是一种细胞外基质蛋白,在体内平衡中具有关键功能,与癌症和纤维化等疾病的发病机制有关。我们利用这种示踪剂对小鼠进行了生物分布和 SPECT/CT 研究,并对小鼠子宫组织和患者子宫内膜异位症组织进行了免疫组化染色。在使用放射性示踪剂[111In]In-FnBPA5进行的生物分布和SPECT/CT研究中,我们发现子宫肌层对放射性示踪剂的摄取随小鼠发情周期的变化而变化,在雌激素依赖阶段,[111In]In-FnBPA5的摄取量较高,这表明当雌激素水平较高时,松弛的纤维连接蛋白丰度增加。最后,对患者样本进行的免疫组化分析表明,子宫内膜异位基质附近的纤维粘连蛋白优先松弛:结论:以高雌激素水平为特征的雌激素周期阶段会导致小鼠子宫肌层中的松弛纤维粘连蛋白含量增加。这一发现以及利用人体子宫内膜异位症组织进行的首次概念验证研究表明,松弛纤维粘连蛋白可能是开发针对子宫内膜异位症病变的诊断放射性示踪剂的潜在靶点。与[111In]In-FnBPA5相匹配的靶向分子正在进行临床前开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Relaxed fibronectin: a potential novel target for imaging endometriotic lesions.

Background: Endometriosis is characterized by the ectopic occurrence of endometrial tissue. Though considered benign, endometriotic lesions possess tumor-like properties such as tissue invasion and remodeling of the extracellular matrix. One major clinical hurdle concerning endometriosis is its diagnosis. The diagnostic modalities ultrasound and MRI are often unable to detect all lesions, and a clear correlation between imaging and clinical symptoms is still controversial. Therefore, it was our aim to identify a potential target to image active endometriotic lesions.

Results: For our studies, we employed the preclinical radiotracer [111In]In-FnBPA5, which specifically binds to relaxed fibronectin-an extracellular matrix protein with key functions in homeostasis that has been implicated in the pathogenesis of diseases such as cancer and fibrosis. We employed this tracer in biodistribution as well as SPECT/CT studies in mice and conducted immunohistochemical stainings on mouse uterine tissue as well as on patient-derived endometriosis tissue. In biodistribution and SPECT/CT studies using the radiotracer [111In]In-FnBPA5, we found that radiotracer uptake in the myometrium varies with the estrous cycle of the mouse, leading to higher uptake of [111In]In-FnBPA5 during estrogen-dependent phases, which indicates an increased abundance of relaxed fibronectin when estrogen levels are high. Finally, immunohistochemical analysis of patient samples demonstrated that there is preferential relaxation of fibronectin in the proximity of the endometriotic stroma.

Conclusion: Estrous cycle stages characterized by high estrogen levels result in a higher abundance of relaxed fibronectin in the murine myometrium. This finding together with a first proof-of-concept study employing human endometriosis tissues suggests that relaxed fibronectin could be a potential target for the development of a diagnostic radiotracer targeting endometriotic lesions. With [111In]In-FnBPA5, the matching targeting molecule is in preclinical development.

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来源期刊
EJNMMI Research
EJNMMI Research RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-
CiteScore
5.90
自引率
3.10%
发文量
72
审稿时长
13 weeks
期刊介绍: EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies. The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.
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