Intracolic ultrasound molecular imaging: a novel method for assessing colonic tumor necrosis factor-α expression in inflammatory bowel disease

While anti-tumor necrosis factor alpha (TNF-α) therapy has been proven effective in inflammatory bowel disease (IBD), approximately 40% of patients lose the response. Transmembrane TNF-α (mTNF-α) expression in the intestinal mucosa is correlated with therapeutic efficacy, and quantification of mTNF-α expression is significant for predicting response. However, conventional intravenous application of microbubbles is unable to assess mTNF-α expression in intestinal mucosa. Herein, we proposed intracolic ultrasound molecular imaging with TNF-α-targeted microbubbles (MB ) to quantitatively detect mTNF-α expression in the intestinal mucosa. MB was synthesized via a biotin-streptavidin bridging method. TNF-α-targeted ultrasound imaging was performed by intracolic application of MB to detect mTNF-α expression in surgical specimens from a murine model and patients with IBD. Linear regression analyses were performed to confirm the accuracy of quantitative targeted ultrasound imaging. On quantitative TNF-α-targeted ultrasound images, a greater signal intensity was observed in the mouse colons with colitis ([1.96 ± 0.45] × 10 a.u.) compared to that of the controls ([0.56 ± 0.21] × 10 a.u., P