Detection of Intestinal Inflammation by Vascular Adhesion Protein-1-Targeted [68Ga]Ga-DOTA-Siglec-9 Positron Emission Tomography in Murine Models of Inflammatory Bowel Disease

Achol A Bhowmik, Taina R H Heikkilä, Lauri Polari, Jenni Virta, Heidi Liljenbäck, Olli Moisio, Xiang-Guo Li, Riikka Viitanen, Sirpa Jalkanen, Jukka Koffert, Diana M Toivola, Anne Roivainen

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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 [ 68Ga]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 [ 68Ga]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 [ 68Ga]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 [ 68Ga]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 [ 68Ga]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 [ 68Ga]Ga-DOTA-Siglec-9 in diagnosis and monitoring of the disease are warranted.

Original languageEnglish
Number of pages12
JournalMolecular Imaging and Biology
DOIs
Publication statusE-pub ahead of print - 18 Dec 2023
MoE publication typeA1 Journal article-refereed

Keywords

  • Inflammatory bowel disease
  • Murine colitis ·
  • Positron emission tomography
  • Vascular adhesion protein-1
  • Siglec-9 · [68Ga]Ga-DOTA-Siglec-9

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