PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model

Abstract

Monoclonal antibodies targeting tumor necrosis factor-alpha (antiTNF-α) are used for patients with immuno-mediated illness as inflammatory bowel disease (IBD). However, 20–40 % of IBD patients do not respond to these therapies, and increasing knowledge of biodistribution could optimize their use and consequently their effectiveness. The aim of this study is to compare the biodistribution of adalimumab after intravenous (IV) and subcutaneous (SC) administration using Positron Emission Tomography (PET) imaging in IBD animal models. IBD was induced in mice using oral dextran sulfate sodium (DSS) and each induced animal was individually confirmed using [¹⁸F]FDG PET/CT scans, weight monitoring and histopathological analysis of colon tissue samples. The SC and IV biodistribution pharmacokinetics profiles and in vivo biodistribution of adalimumab labeled with ⁸⁹Zr were evaluated using a dedicated PET/CT scanner. Mean standardized uptake values (SUV) were estimated from the colon, liver, and blood over seven days. Blood analysis revealed faster elimination of adalimumab in IBD models compared to controls, and after IV compared to SC administration (SUV 168 h p.i. SC-IBD = 0.06 ± 0.02, SC-Control = 1.08 ± 0.11, IV-IBD = 0.02 ± 0.01, IV-Control = 0.26 ± 0.13). Furthermore, IBD models exhibited faster whole-body clearance than controls and an earlier and higher concentration peak of adalimumab in the colon after IV (SUV 6 h p.i. IBD-IV = 2.11 ± 0.18) compared to SC administration (SUV 24 h p.i. IBD-SC = 1.49 ± 0.27). Our findings demonstrate the significant influence of the administration route and the TNF-α expression (local and also systemic) on the amount of adalimumab reaching the colon over time.