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

克罗恩病(CD)是一种慢性炎症性疾病，可影响肠道的任何部位，目前尚无治愈方法。它影响着全球680万人，英国每年的医疗费用超过10亿GB。最近的数据表明，尽管过去20年来在帮助控制疾病的治疗方面取得了重大进展，但多达一半的患者仍然发展为进行性肠道疤痕，需要手术治疗，高达70%的患者在确诊后10年内需要手术。不幸的是，这并不是治愈的方法，有些人仍然需要再次手术。这些特征对个人的教育、工作和社交生活都有毁灭性的影响。保持健康的、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消炎，但还没有针对瘢痕形成(纤维化)、其活动及其进展的治疗方法。我们在CD抗疤痕治疗和推进护理方面取得进展的一个主要障碍是，我们无法使用非侵入性测试准确地识别肠道疤痕；这对于开发预防永久性肠道损伤的新疗法至关重要。虽然有几种测试可以对肠道进行成像，包括计算机断层扫描(CT)、超声波和磁共振成像(MRI)，但还没有技术来衡量瘢痕形成(纤维化)过程随着时间的推移有多活跃。目前的检测不能预测CD患者的瘢痕形成进展和最终的手术。因此，目前的管理是“被动的”，处理的是随着时间的推移而出现的并发症，而不是“主动的”，旨在预防纤维化和最终的手术。我们在诊断学和疾病相关风险分层方面的局限性也限制了我们在这一领域开发抗瘢痕疗法的进展。我处于一个独特的位置来研究一种新的方法，这种方法可以识别疤痕活动并跟踪进行性肠道损伤，而不需要侵入性测试。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物(FAPI)，它可以跟踪疤痕形成及其在肠道中的活动。可以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)来检测疤痕区域内FAPI的存在和数量。我们的合作伙伴之前的工作表明，这种方法可以检测到心脏、肺和肾脏中的疤痕，但这还没有在肠道中进行研究。如果成功，这项研究将是第一个检测CD瘢痕活动的方法，并有可能彻底改变这种疾病的治疗方法。这项工作的成果可以促进新药开发，以阻止瘢痕形成(纤维化)的过程，并改善CD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.