Work

Development of a toxin-selective immunotracer for in vivo detection of Clostridioides difficile infection by immunoPET

Year: 2025

Type: article

Abstract: Background: Clostridioides difficile infection (CDI) is a major healthcare challenge, associated with high morbidity and mortality. Current diagnostic methods have limitations in specificity and invasiveness, necessitating the development of novel, non-invasive imaging techniques. This study aims to develop and evaluate an immunoPET radiotracer targeting C. difficile toxin B for in vivo CDI detection in mice model. Results: Monoclonal antibody, Bezlotoxumab, was radiolabeled with [125I]I for in vitro characterization and [89Zr]Zr for in vivo PET imaging, resulting in high radiochemical yields (75.36 ± 4.11 % for [125I]I and 71.58 ± 8.19 % for [89Zr]Zr) and purities (>99.99 % both cases), with stable binding properties. PET/CT imaging 48h post infection in an animal model of CDI (C57BL/6 mice employing ribotype 027 strain) demonstrated specific accumulation of [89Zr]Zr-DFO-Beztxab in the colon and cecum of infected mice, distinguishing CDI from dysbiosis and healthy controls, and confirmed by PET quantification and ex vivo biodistribution. Conclusions: We successfully developed an immunoPET radiotracer targeting toxin B for CDI detection. Its application in a CDI animal model proved its capacity to detect the source of infection with high specificity, avoiding sterile inflammation.

Source: EJNMMI Radiopharmacy and Chemistry

DOI: 10.1186/s41181-025-00350-x