Fibrosis Associated Protein Inhibitor (FAPI) radiotracer-based imaging to identify fibrosis activity in intestinal Crohn's Disease (FATE-CD)

克罗恩病（CD）是一种慢性炎症，可以影响肠道的任何部分，目前还没有治愈方法。它影响着全球680万人，英国每年的医疗费用超过10亿英镑。最近的数据表明，尽管在过去20年里，在帮助控制疾病的治疗方面取得了重大进展，但仍有多达一半的患者出现进行性肠瘢痕形成，需要手术治疗，而在确诊后的10年内，高达70%的患者需要手术治疗。不幸的是，这并不能治愈，有些人仍然需要重复手术。这些特征对个人的教育、工作和社会生活都有毁灭性的影响。保持健康且没有疾病的小肠长度对于预防肠道衰竭和死亡的长期风险至关重要。我们目前的治疗重点是解决炎症，但没有针对疤痕（纤维化），其活动和进展的治疗。我们在抗瘢痕形成治疗和推进乳糜泻护理方面取得进展的一个主要障碍是我们无法通过非侵入性检查准确识别肠道瘢痕形成；这对于开发防止永久性肠道损伤的新疗法至关重要。虽然有几种方法可以对肠道进行成像，包括计算机断层扫描（CT）、超声和磁共振成像（MRI），但没有技术可以测量疤痕（纤维化）过程随着时间的推移有多活跃。目前的测试不能预测CD患者的疤痕进展和最终手术。因此，目前的管理是“反应性的”，处理随时间出现的并发症，而不是“前瞻性的”，旨在预防纤维化和最终手术。我们在诊断和疾病相关风险分层方面的局限性也限制了我们在该领域开发抗疤痕疗法的进展。我处于一个独特的位置来研究一种新的方法，可以识别疤痕活动和跟踪进展性肠损伤，而不需要侵入性检查。在这项研究中，我建议使用一种“染料”，也被称为纤维化相关蛋白抑制剂（FAPI），它可以跟踪疤痕及其在肠道中的活动。使用我们目前的成像测试（正电子发射断层扫描和磁共振成像：PET/MRI）可以检测疤痕区域内FAPI的存在和数量。我们的合作伙伴之前的工作表明，这种方法可以检测心脏、肺和肾脏内的疤痕，但还没有在肠道中进行过研究。如果成功，这项研究将是第一个检测CD中疤痕活性的方法，并有可能彻底改变这种情况的护理。这项工作的成果可以促进新药的开发，以停止瘢痕形成（纤维化）的过程，并改善乳糜泻患者的预后。

Crohn's Disease (CD) is a chronic inflammatory condition that can affect any part of the intestine and currently has no cure. It affects 6.8 million people worldwide with UK healthcare costs in excess of £1 billion per year. Recent data suggests that the despite significant progress in treatments over the last 2 decades to help control disease, upto half of patients still develop progressive bowel scarring that require surgery and upto 70% needing surgery within a 10 years from diagnosis. Unfortunately this is not a cure and some still require repeat surgery. These features have a devastating impact on an individual including education, work and social life. Preservation of a healthy length of small bowel that is free of disease is critical to prevent the long term risk of gut failure and death. Our current treatments focus on resolving inflammation but there are no treatments targeting scarring (fibrosis), its activity and its progression. A major hurdle in our progress towards anti-scarring treatments and advancing care in CD has been our inability to identify bowel scarring accurately using non-invasive tests; this being critical in developing new treatments that prevent permanent bowel damage. Although several tests are available to image the gut including computed tomography (CT), ultrasound and magnetic resonance imaging (MRI), there are no techniques to measure how active the scarring (fibrosis) process is over time. Current tests cannot predict scarring progression and eventual surgery in patients with CD. Therefore current management is 'reactive', dealing with complications that arise over time rather than 'proactive' aiming to prevent fibrosis and eventual surgery. Our limitations in diagnostics and disease related risk stratification has also limited our progress in developing anti-scarring therapies in this field. I am in a unique position to investigate a novel method that can identify scarring activity and track progressive bowel damage without the need for invasive tests. In this study I propose to use a 'dye', also known as fibrosis associated protein inhibitor (FAPI), that tracks scarring and its activity in the gut. The presence and amount of FAPI within an area of scarring can be detected using our current imaging tests (positron emission tomography and Magnetic resonance imaging: PET/MRI). Previous work from our partners have shown that this method can detect scarring within the heart, lungs and kidneys but this has not been studied in the intestine. If successful, this study will be the first method for detecting scarring activity in CD and have the potential to revolutionise care for this condition. Output from this work could facilitate new drug development to halt the processing of scarring (fibrosis) and improve the outcomes for patients with CD.