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

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.

Crohn's disease (CD) is a chronic inflammatory disorder that can affect any part of the intestinal tract. CD affects 6.8 million people worldwide with rising global prevalence and UK healthcare costs in excess £1 billion/year. A significant 50% of CD patients with predominant small bowel disease (ileum) develop scarring (fibrosis) and intestinal obstruction, with upto 70% requiring intestinal surgery within 10 years of their initial diagnosis, and upto 1/3rd require repeat surgery for stricture recurrence. Preservation of a healthy length of functioning small bowel that is free of disease, is critical to prevent the risk of long term intestinal failure and death. Myofibroblasts play a critical role in fibrosis and have been shown to express fibroblast activated protein (FAP) across several organ specific disorders including rheumatoid arthritis, ischaemic heart disease and fibrosed intestine in CD and represents a marker of fibrosis activity.
There are currently no drugs that can prevent or reverse fibrosis in CD and one of the critical limitation in drug development is our inability to track fibrosis and assess response to current and future treatments with our current tests. Although several imaging tests can help identify stricturing (end-result of severe fibrosis) in CD including magnetic resonance imaging (MRI), they cannot quantify fibrosis and its activity and help predict subsequent disease progression. In this study I propose to investigate the clinical utility of fibrosis activated protein inhibitor (FAPI) PET/MRI to identify intestinal fibrosis activity in CD and investigate its clinical utility in predicting fibrosis progression and subsequent intestinal surgery. FAPI PET/MRI has been used to assess for fibrosis activity across a range of organ system including the heart, lung and kidneys. If successful, this study will be the first method for imaging intestinal fibrosis and a major scientific advance in the field of CD.