Granzyme B, a serine protease, is a key effector molecule in the immune system that facilitates the targeted destruction of infected or malignant cells. It also serves as a biomarker for cellular activation. Utilizing this property, researchers have developed granzyme B positron emission tomography (PET), which has proven effective in monitoring the response to immunotherapy. A recent study shows that granzyme B PET can non-invasively detect inflammatory bowel disease (IBD) and provide a real-time view of tissue inflammation. Published in the Journal of Nuclear Medicine, this study suggests that this method could revolutionize IBD monitoring and treatment, potentially leading to more personalized patient management strategies.
IBD, a chronic inflammatory disorder of the gastrointestinal tract, includes two main types namely Crohn’s disease and ulcerative colitis. Despite advances in clinical management, challenges remain in improving diagnostic accuracy, managing treatment intolerance, and addressing the recurring cycles of remission and relapse. Moreover, long-term IBD increases the risk of cancer, necessitating continuous monitoring of disease activity. Granzyme B PET offers a promising solution to these challenges by providing high-resolution, non-invasive imaging that captures immune system activation in real-time, thereby enhancing diagnostic precision and improving treatment outcomes for patients with IBD. Currently, there is no accurate method to detect and differentiate active inflammation from chronic disease. MRI and CT scans focus on structural changes in the bowel, while other imaging techniques detect an increased number of immune cells in the tissue. However, none of these tools capture the dynamic nature of immune responses in the colon.
Heidari and colleagues explored the potential of the granzyme B gene as a biomarker for detecting IBD and predicting treatment responses. The study involved staining human tissue samples of Crohn’s disease and ulcerative colitis both active and inactive and noninflamed bowel tissue to measure granzyme B expression. Diseased tissues showed a significant upregulation of granzyme B compared to noninflamed tissues, with active disease exhibiting higher levels than inactive disease. Additionally, tissue samples from IBD treatment responders and non-responders revealed lower granzyme B expression in responders.
The researchers further investigated granzyme B expression changes in a murine model, including colitis-induced and control mice. Using 68Ga-NOTA-GZP PET imaging at one, three, and four weeks, they observed a significantly increased bowel uptake of 68Ga-NOTA-GZP in colitis-induced mice compared to controls. Post-treatment, the uptake in colitis-induced mice decreased, although it remained significantly higher than in control mice at all times. The researchers emphasized that the granzyme B PET can facilitate the timely detection of active disease, determine the need to initiate treatment and monitor the response to treatment, ensuring the resolution of inflammation. This is particularly crucial for monitoring inflammation in bowel areas that are inaccessible for endoscopy and tissue sampling.
Heidari et.al. highlighted the unique capabilities of granzyme B PET, noting its potential to significantly alter disease trajectories through close monitoring of treatment efficacy, embodying the essence of precision medicine. This new tool offers a promising solution to the ongoing challenges in IBD management by providing high-resolution, non-invasive imaging that captures immune system activation in real time. By enhancing diagnostic precision and offering a more dynamic assessment of immune responses, granzyme B PET stands to improve treatment outcomes and quality of life for patients with IBD, paving the way for more personalized and effective management strategies.
References
- Heidari P, Haj-Mirzaian A, Prabhu S, Ataeinia B, Esfahani SA, Mahmood U. Granzyme B PET Imaging for Assessment of Disease Activity in Inflammatory Bowel Disease. Journal of Nuclear Medicine. 2024 Jul 1;65(7):1137–43.
- Capaccione KM, Doubrovin M, Bhatt N, Mintz A, Molotkov A. Granzyme B PET Imaging of the Innate Immune Response. Molecules. 2020 Jul 7;25(13):3102