AI Article Synopsis
- The study investigates the use of VAP-1-targeted PET imaging with the tracer [Ga]Ga-DOTA-Siglec-9 to assess inflammation in mouse models of inflammatory bowel disease (IBD).
- Two mouse models, K8 and C57Bl/6NCrl, were tested to measure the uptake of the tracer, indicating increased levels of intestinal inflammation compared to controls.
- Results showed that the VAP-1 tracer could effectively visualize inflammation, suggesting potential for non-invasive imaging of IBD in future patient studies.
Article Abstract
Purpose: Inflammatory bowel disease (IBD) can be imaged with positron emission tomography (PET), but existing PET radiopharmaceuticals have limited diagnostic accuracy. Vascular adhesion protein-1 (VAP-1) is an endothelial cell surface molecule that controls leukocyte extravasation into sites of inflammation. However, the role of inflammation-induced VAP-1 expression in IBD is still unclear. Therefore, this study investigated the utility of VAP-1-targeted [Ga]Ga-DOTA-Siglec-9 positron emission tomography/computed tomography (PET/CT) for assessing inflammation in two mouse models of IBD.
Procedures: Studies were performed using K8 mice that develop a chronic colitis-phenotype and C57Bl/6NCrl mice with acute intestinal inflammation chemically-induced using 2.5% dextran sodium sulfate (DSS) in drinking water. In both diseased and control mice, uptake of the VAP-1-targeting peptide [Ga]Ga-DOTA-Siglec-9 was assessed in intestinal regions of interest using in vivo PET/CT, after which ex vivo gamma counting, digital autoradiography, and histopathological analyses were performed. Immunofluorescence staining was performed to determine VAP-1-expression in the intestine, including in samples from patients with ulcerative colitis.
Results: Intestinal inflammation could be visualized by [Ga]Ga-DOTA-Siglec-9 PET/CT in two murine models of IBD. In both models, the in vivo PET/CT and ex vivo studies of [Ga]Ga-DOTA-Siglec-9 uptake were significantly higher than in control mice. The in vivo uptake was increased on average 1.4-fold in the DSS model and 2.0-fold in the K8 model. Immunofluorescence staining revealed strong expression of VAP-1 in the inflamed intestines of both mice and patients.
Conclusions: This study suggests that the VAP-1-targeting [Ga]Ga-DOTA-Siglec-9 PET tracer is a promising tool for non-invasive imaging of intestinal inflammation. Future studies in patients with IBD and evaluation of the potential value of [Ga]Ga-DOTA-Siglec-9 in diagnosis and monitoring of the disease are warranted.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973022 | PMC |
| http://dx.doi.org/10.1007/s11307-023-01885-8 | DOI Listing |
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