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Molecular Imaging and Biology
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Open Access 18-12-2023 | Positron Emission Tomography | Research Article

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

Authors: 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

Published in: Molecular Imaging and Biology | Issue 2/2024

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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.
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Metadata
Title
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
Authors
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
Publication date
18-12-2023
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 2/2024
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-023-01885-8

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