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

基于纤维化相关蛋白抑制剂 (FAPI) 的放射性示踪成像，可识别肠道克罗恩病 (FATE-CD) 中的纤维化活动

• 批准号: MR/X030784/1
• 负责人: Rahul Kalla
• 金额: $ 30.84万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX030784%2F1
• 关键词: Fibrosis; Associated; Protein; Inhibitor; FAPI

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.

克罗恩病（CD）在全球范围内，英国的医疗保健费用超过每年10亿英镑，在过去的20年中。不幸的是，在10年内需要手术，这是一种治疗方法，其中一些需要重复手术，这些特征具有疾病，对肠道失败的长期风险至关重要。我们目前的治疗方法集中在靶向炎症（纤维化），其活性和进步肠道损伤的新处理。随着时间的流逝，出现的并发症，而不是在诊断和疾病相关的风险分层方面进行纤维化和最终的手术。为了鉴定疤痕活性和侵入性测试的新方法，我向我们提出了侵入性测试。可以使用当前的成像测试来检测疤痕（正电子发射断层扫描和磁共振成像：PET/MRI）。并有可能彻底改变对工作工作的护理护理，这可能促进新的发展，以阻止疤痕（FIROSIS）的处理并改善CD患者的结局。