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

Mol Med. 2021 Sep 23;27(1):119. doi: 10.1186/s10020-021-00379-z.

Abstract

Background: 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 (MBTNF-α) to quantitatively detect mTNF-α expression in the intestinal mucosa.

Methods: MBTNF-α was synthesized via a biotin-streptavidin bridging method. TNF-α-targeted ultrasound imaging was performed by intracolic application of MBTNF-α 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.

Results: On quantitative TNF-α-targeted ultrasound images, a greater signal intensity was observed in the mouse colons with colitis ([1.96 ± 0.45] × 106 a.u.) compared to that of the controls ([0.56 ± 0.21] × 106 a.u., P < 0.001). Targeted US signal intensities and inflammatory lesions were topographically coupled in mouse colons. Linear regression analyses in specimens of mice and patients demonstrated significant correlations between the targeted ultrasound signal intensity and mTNF-α expression (both P < 0.001). Furthermore, TNF-α-targeted ultrasound imaging qualitatively distinguished the varying inflammatory severity in intestinal specimens from IBD patients.

Conclusion: Intracolic ultrasound molecular imaging with MBTNF-α enables quantitative assessment of mTNF-α expression. It may be a potential tool for facilitating the implementation of personalized medicine in IBD.

Keywords: Inflammatory bowel disease; Intracolic ultrasound molecular imaging; Targeted microbubbles; Tumor necrosis factor alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / diagnostic imaging*
  • Colitis / metabolism
  • Colon / diagnostic imaging*
  • Colon / metabolism
  • Colon / pathology
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Gene Expression
  • Humans
  • Inflammatory Bowel Diseases / diagnostic imaging*
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Intestinal Mucosa / diagnostic imaging*
  • Intestinal Mucosa / metabolism
  • Linear Models
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trinitrobenzenesulfonic Acid
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Ultrasonography / methods*

Substances

  • Tumor Necrosis Factor-alpha
  • Trinitrobenzenesulfonic Acid