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Predicting Therapeutic Response by in vivo Molecular Imaging in Inflammatory Bowel Diseases

机译:通过体内分子成像预测炎症性肠病的治疗反应

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Background: Different invasive and non-invasive imaging modalities are indispensable tools in the management of inflammatory bowel disease (IBD) patients. Standard imaging procedures like white light endoscopy or MRI are used to define gut inflammation based on structural changes and altered morphology of the mucosa. Nevertheless, it has thus far not been possible to analyse biological processes at the cellular level, which drive intestinal inflammation in IBD patients. The recent advent of molecular imaging in the field of IBD has opened new promising avenues to allow personalized medicine approaches based on in vivo-detected molecular findings. Key Messages: Recent clinical studies have attempted to address the issue of predicting therapeutic response to anti-tumor necrosis factor (TNF) treatment in IBD patients based on the molecular mechanism of action of these agents and corresponding in vivo assessment of mucosal immune responses. Several experimental studies have indicated that one of the main functions of efficacious anti-TNF therapy in IBD is the induction of intestinal cell apoptosis. Fittingly, a corresponding molecular-imaging study using single-photon emission CT for the localization and quantification of cell apoptosis, demonstrated that induction of mucosal T-cell apoptosis correlated with the therapeutic response to anti-TNF therapy in Crohn's disease patients. There was moreover a predictive capacity regarding therapeutic efficacy. As the main biological properties of anti-TNF antibodies in IBD are mediated through binding to membrane-bound TNF (mTNF) expressing intestinal cells, another study used molecular imaging for in vivo visualization of these cells via fluorescent anti-TNF antibodies to predict therapeutic efficacy of these agents. It could be shown that patients with high amounts of mTNF positive cells showed significantly better response rates compared to patients with low amounts of mTNF positive cells. Conclusion: In vivo molecular imaging in IBD has the potential to have an impact on our current treatment approaches and may allow us to individualize specific therapies based on molecular level analysis. (C) 2016 S. Karger AG, Basel
机译:背景:在治疗炎症性肠病(IBD)患者时,不同的有创和无创成像方式是必不可少的工具。标准的成像程序(如白光内窥镜检查或MRI)用于根据粘膜的结构变化和改变的形态来定义肠道炎症。然而,迄今为止,尚不可能在细胞水平上分析导致IBD患者肠道炎症的生物学过程。 IBD领域中分子成像的最新出现开辟了新的有前途的途径,以允许基于体内检测到的分子发现的个性化医学方法。关键信息:最近的临床研究已尝试基于这些药物的分子作用机理以及相应的体内对粘膜免疫反应的评估,来预测IBD患者对抗肿瘤坏死因子(TNF)治疗反应的预测问题。几项实验研究表明,有效的抗TNF治疗IBD的主要功能之一是诱导肠道细胞凋亡。适当地,使用单光子发射CT对细胞凋亡进行定位和定量的相应分子成像研究表明,粘膜T细胞凋亡的诱导与克罗恩病患者抗TNF治疗的治疗反应相关。此外,关于治疗功效具有预测能力。由于IBD中抗TNF抗体的主要生物学特性是通过与表达膜结合TNF(mTNF)的肠道细胞结合而介导的,因此另一项研究使用分子成像技术通过荧光抗TNF抗体在体内可视化这些细胞,从而预测治疗效果这些代理商。可以证明,与mTNF阳性细胞较少的患者相比,mTNF阳性细胞大量的患者显示出明显更好的应答率。结论:IBD中的体内分子成像可能会影响我们目前的治疗方法,并可能使我们能够根据分子水平分析来个性化特定疗法。 (C)2016 S.Karger AG,巴塞尔

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