Molecular imaging of liver inflammation using an anti-VCAM-1 nanobody

Nat Commun. 2023 Feb 24;14(1):1062. doi: 10.1038/s41467-023-36776-7.

Abstract

To date, a biopsy is mandatory to evaluate parenchymal inflammation in the liver. Here, we evaluated whether molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) could be used as an alternative non-invasive tool to detect liver inflammation in the setting of chronic liver disease. To do so, we radiolabeled anti-VCAM-1 nanobody (99mTc-cAbVCAM1-5) and used single-photon emission computed tomography (SPECT) to quantify liver uptake in preclinical models of non-alcoholic fatty liver disease (NAFLD) with various degree of liver inflammation: wild-type mice fed a normal or high-fat diet (HFD), FOZ fed a HFD and C57BL6/J fed a choline-deficient or -supplemented HFD. 99mTc-cAbVCAM1-5 uptake strongly correlates with liver histological inflammatory score and with molecular inflammatory markers. The diagnostic power to detect any degree of liver inflammation is excellent (AUROC 0.85-0.99). These data build the rationale to investigate 99mTc-cAbVCAM1-5 imaging to detect liver inflammation in patients with NAFLD, a largely unmet medical need.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat
  • Hepatitis* / pathology
  • Inflammation / pathology
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Molecular Imaging / methods
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Vascular Cell Adhesion Molecule-1