Objective Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo-800CW, and identify its target cells using fluorescence molecular imaging (FMI). Design Forty three FMI procedures were performed, which consisted of macroscopic in vivo assessment during endoscopy, followed by macroscopic and microscopic ex vivo imaging. In phase A, patients received an intravenous dose of 4.5 mg, 15 mg vedo-800CW or no tracer prior to endoscopy. In phase B, patients received 15 mg vedo-800CW preceded by an unlabelled (sub)therapeutic dose of vedolizumab. Results FMI quantification showed a dose-dependent increase in vedo-800CW fluorescence intensity in inflamed tissues, with 15 mg (153.7 au (132.3–163.7)) as the most suitable tracer dose compared with 4.5 mg (55.3 au (33.6–78.2)) (p=0.0002). Moreover, the fluorescence signal decreased by 61% when vedo-800CW was administered after a therapeutic dose of unlabelled vedolizumab, suggesting target saturation in the inflamed tissue. Fluorescence microscopy and immunostaining showed that vedolizumab penetrated the inflamed mucosa and was associated with several immune cell types, most prominently with plasma cells. Conclusion These results indicate the potential of FMI to determine the local distribution of drugs in the inflamed target tissue and identify drug target cells, providing new insights into targeted agents for their use in IBD. Trial registration number [NCT04112212][1]. Data are available upon reasonable request. The main data supporting the outcomes of this clinical trial are available within the manuscript and its supplementary materials. The study protocol is included as a data supplement available with the online version of this article. Deidentified raw FMI data may be obtained after publication by sending an email to the corresponding author including a clear research proposal. Data requestors will need to sign a data access agreement in order to gain access. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04112212&atom=%2Fgutjnl%2Fearly%2F2024%2F04%2F05%2Fgutjnl-2023-331696.atom

中文翻译：

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荧光标记的维多珠单抗可可视化炎症性肠病中的药物分布和粘膜靶细胞

目的 改善 IBD 中维多珠单抗等生物疗法的患者选择和开发需要透彻了解作用机制和靶点结合，从而提供个体化治疗策略。我们的目的是可视化静脉注射的荧光标记维多珠单抗 vedo-800CW 的宏观和微观分布，并使用荧光分子成像 (FMI) 识别其靶细胞。设计 进行了 43 次 FMI 程序，其中包括内窥镜检查期间的宏观体内评估，以及随后的宏观和微观离体成像。在 A 阶段，患者在内窥镜检查前接受静脉注射 4.5 mg、15 mg vedo-800CW 或不接受示踪剂。在 B 期，患者接受 15 mg vedo-800CW，然后接受未标记的（亚）治疗剂量的维多珠单抗。结果 FMI 定量显示发炎组织中 vedo-800CW 荧光强度呈剂量依赖性增加，与 4.5 mg (55.3 au (33.6–78.2)) 相比，15 mg (153.7 au (132.3–163.7)) 是最合适的示踪剂剂量（p=0.0002）。此外，在未标记的维多珠单抗治疗剂量后施用 vedo-800CW 时，荧光信号减少了 61%，表明发炎组织中的目标饱和。荧光显微镜和免疫染色显示，维多珠单抗穿透发炎的粘膜，并与多种免疫细胞类型相关，最显着的是与浆细胞相关。结论 这些结果表明 FMI 有潜力确定药物在发炎靶组织中的局部分布并识别药物靶细胞，为靶向药物在 IBD 中的应用提供新的见解。试用注册号[NCT04112212][1]。数据可根据合理要求提供。支持该临床试验结果的主要数据可在手稿及其补充材料中找到。该研究方案作为数据补充包含在本文的在线版本中。发表后，可以通过向相应作者发送电子邮件（包括明确的研究计划）来获得去识别化的原始 FMI 数据。数据请求者需要签署数据访问协议才能获得访问权限。 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04112212&atom=%2Fgutjnl%2Fearly%2F2024%2F04%2F05%2Fgutjnl-2023-331696.atom