In vivo endoscopic molecular imaging to predict therapeutic response to anti-adhesion molecule therapy in Crohn's disease patients

生物疗法的出现极大地提高了我们治疗克罗恩病患者的可能性。然而，大约40%的人对这些代理没有反应。因此，寻找生物治疗反应的预测指标具有很高的临床意义。在先前的研究中，我们证明了在共聚焦激光内窥镜检查中，局部注射荧光抗肿瘤坏死因子抗体可以检测到肠道mtnf+免疫细胞。Mtnf+细胞数量高的患者与mtnf+细胞数量低的患者相比，在随后的抗肿瘤坏死因子治疗中表现出显著更高的反应。本研究的目的是用一种针对A4？7整合素的荧光抗黏附分子抗体，通过内窥镜分子成像技术对克罗恩病患者体内的A4？7黏附分子细胞进行可视化。A4？7+细胞的数量将与抗-A4？7抗体治疗的临床反应相关，并可能作为预测疗效的生物标记物。这些数据可能进一步表明，带有荧光抗体的分子成像具有预测生物治疗的治疗反应的潜力，并为克罗恩病的个性化药物开辟了新的途径。

The advent of biological therapies has greatly enhanced our therapeutic possibilities In Crohn's disease patients. However, about 40% do not respond to these agents. It is therefore of high clinical relevance to find a predictor for response to biological treatment. In a previous study we demonstrated that topical administration of a fluorescent anti-TNF antibody led to the detection of Intestinal mTNF+ Immune cells during confocal laser endomicroscopy. Patients with high amounts of mTNF+ cells showed significantly higher response upon subsequent anti-TNF therapy compared to patients with low amounts of mTNF+ cells. Aim of the proposed study is the in vivo visualization of a4ß7 bearing mucosal cells in Crohn's disease patients by an endoscopic molecular Imaging procedure with a fluorescent ant-adhesion molecule antibody directed against the a4ß7 integrin. The amount of a4ß7+ cells will be correlated to the clinical response to therapy with an antl-a4ß7 antibody and might serve as a predictive biomarker regarding therapeutic efficacy. These data could further indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatments and open new avenues for personalized medicine in Crohn's disease.