Evaluating [(11)C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis

PURPOSE: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that affects an increasing number of patients. High comorbidity is observed between UC and other diseases in which inflammation may be involved, including brain diseases such as cognitive impairment, mental disorders, anxiety, and depression. To investigate the increased occurrence of these brain diseases in patients with UC, non-invasive methods for monitoring peripheral and central inflammation could be applied. Therefore, the goal of this study is to assess the feasibility of monitoring gut and brain inflammation in a rat model of chemically induced colitis by positron emission tomography (PET) with [(11)C]PBR28, a tracer targeting the translocator protein (TSPO), which is upregulated when microglia and macrophages are activated. PROCEDURES: Colitis was induced in rats by intra-rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats with colitis and healthy control animals were subjected to [(11)C]PBR28 PET of the abdomen followed by ex vivo biodistribution in order to assess whether inflammation in the gut could be detected. Another group of rats with colitis underwent repetitive [(11)C]PBR28 PET imaging of the brain to investigate the development of neuroinflammation. RESULTS: Eleven days after TNBS injection, ex vivo biodistribution studies demonstrated increased [(11)C]PBR28 uptake in the inflamed cecum and colon of rats with colitis as compared to healthy controls, whereas PET imaging did not show any difference between groups at any time. Similarly, repetitive PET imaging of the brain did not reveal any neuroinflammation induced by the TNBS administration in the colon. In contrast, significantly increased [(11)C]PBR28 uptake in cerebellum could be detected in ex vivo biodistribution studies on day 11. CONCLUSION: Inflammation in both the gut and the brain of rats with chemically induced colitis was observed by ex vivo biodistribution. However, these effects could not be detected by [(11)C]PBR28 PET imaging in our colitis model, which is likely due to spill-over effects and insufficient resolution of the PET camera.