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

Maxime Nachit, Christopher Montemagno, Romain Clerc, Mitra Ahmadi, François Briand, Sandrine Bacot, Nick Devoogdt, Cindy Serdjebi, Catherine Ghezzi, Thierry Sulpice, Alexis Broisat (), Isabelle A. Leclercq and Pascale Perret
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Maxime Nachit: Institut de Recherche Expérimentale et Clinique, UCLouvain
Christopher Montemagno: Univ. Grenoble Alpes, INSERM, LRB
Romain Clerc: Univ. Grenoble Alpes, INSERM, LRB
Mitra Ahmadi: Univ. Grenoble Alpes, INSERM, LRB
François Briand: Physiogenex
Sandrine Bacot: Univ. Grenoble Alpes, INSERM, LRB
Nick Devoogdt: Vrije Universiteit Brussel
Cindy Serdjebi: Biocellvia
Catherine Ghezzi: Univ. Grenoble Alpes, INSERM, LRB
Thierry Sulpice: Physiogenex
Alexis Broisat: Univ. Grenoble Alpes, INSERM, LRB
Isabelle A. Leclercq: Institut de Recherche Expérimentale et Clinique, UCLouvain
Pascale Perret: Univ. Grenoble Alpes, INSERM, LRB

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36776-7

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