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

生物疗法的出现大大提高了我们治疗克罗恩病患者的可能性。然而，约40%的患者对这些药物没有反应。因此，寻找对生物治疗反应的预测因子具有很高的临床相关性。在之前的一项研究中，我们证明了在共聚焦激光内镜下，局部施用荧光抗tnf抗体导致肠道mTNF+免疫细胞的检测。与mTNF+细胞含量低的患者相比，mTNF+细胞含量高的患者在随后的抗tnf治疗中表现出明显更高的反应。拟议研究的目的是通过内窥镜分子成像程序，使用针对a4ß7整合素的荧光抗粘附分子抗体，对克罗恩病患者携带a4ß7的粘膜细胞进行体内可视化。a4ß7+细胞的数量将与抗l-a4ß7抗体治疗的临床反应相关，并可能作为治疗效果的预测性生物标志物。这些数据可能进一步表明，荧光抗体的分子成像有可能预测对生物治疗的治疗反应，并为克罗恩病的个性化治疗开辟新的途径。

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.