US Molecular Imaging of Acute Ileitis: Anti-Inflammatory Treatment Response Monitored with Targeted Microbubbles in a Preclinical Model

Purpose: To evaluate whether dual-selectin-targeted US molecular imaging allows longitudinal monitoring of anti-inflammatory treatment effects in an acute terminal ileitis model in swine. Materials and Methods: The Institutional Animal Care and Use Committee approved all animal studies. Fourteen swine with chemically induced acute terminal ileitis (day 0) were randomized into the following groups: (a) an anti-inflammatory treatment group (n= 8; meloxicam, 0.25 mg per kilogram of body weight; prednisone, 0.5 mg/kg) and (b) a control group (n= 6; saline). US molecular imaging was performed with a clinical US machine after intravenous injection of clinically translatable dual P-and E-selectin-targeted microbubbles (5 x 10(8)/kg). Three inflamed bowel segments per swine were imaged at baseline, as well as on days 1, 3, and 6 after treatment initiation. At day 6, bowel segments were analyzed ex vivo for selectin expression levels by using quantitative immunofluorescence. Results: After induction of inflammation, US molecular imaging signal increased at day 1 in both animal groups (P<.001). At day 3, signal in the treatment group decreased (P<.001 vs day 1), while signal in control animals did not significantly change (P=.18 vs day 1) and was higher (P=.001) compared with that in the treatment group. At day 6, signal in the treatment group further decreased and remained lower (P=.02) compared with that in the control group. Immunofluorescence confirmed significant (P <=.04) downregulation of both P-and E-selectin expression levels in treated versus control bowel segments. Conclusion: Dual-selectin-targeted US molecular imaging allows longitudinal monitoring of anti-inflammatory treatment effects in a large-animal model of acute ileitis. This supports further clinical development of this quantitative and radiation-free technique for monitoring inflammatory bowel disease. (c) RSNA, 2018