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, Cathérine Ghezzi, Thierry Sulpice, Alexis Broisat, Isabelle Leclercq, Pascale Perret
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 ( 99m Tc-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. 99m Tc-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 99m Tc-cAbVCAM1-5 imaging to detect liver inflammation in patients with NAFLD, a largely unmet medical need.