AUTHOR=Ye Zijian , van der Wildt Berend , Nurmohamed F. Ruben H. A. , van Duyvenbode J. Fred F. Hooning , van Strijp Jos , Vogely H. Charles , Lam Marnix G. E. H. , Dadachova Ekaterina , Weinans Harrie , van der Wal Bart C. H. , Poot Alex J. 

TITLE=Radioimmunotherapy combating biofilm-associated infection in vitro

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1478636

DOI=10.3389/fmed.2024.1478636

ISSN=2296-858X

ABSTRACT=<sec><title>Background</title><p>Addressing prosthetic joint infections poses a significant challenge within orthopedic surgery, marked by elevated morbidity and mortality rates. The presence of biofilms and infections attributed to <italic>Staphylococcus aureus</italic> (<italic>S. aureus</italic>) further complicates the scenario.</p></sec><sec><title>Objective</title><p>To investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections.</p></sec><sec><title>Methods</title><p>Our methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on <italic>S. aureus</italic> and its biofilm. These antibodies were linked with radionuclides actinium-225 (<sup>225</sup>Ac) and lutetium-177 (<sup>177</sup>Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of <italic>S. aureus</italic> and its biofilm to radioimmunotherapy <italic>in vitro</italic>, assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays.</p></sec><sec><title>Results</title><p>Both [<sup>225</sup>Ac]4497-IgG1 and [<sup>177</sup>Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in <italic>S. aureus</italic> in planktonic cultures and biofilms over a 96-h exposure period, compared to non-specific antibody control groups. Specifically, doses of 7.4 kBq and 7.4 MBq of [<sup>225</sup>Ac]4497-IgG1 and [<sup>177</sup>Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [<sup>225</sup>Ac]4497-IgG1 and 14.8 Mbq [<sup>177</sup>Lu]4497-IgG1 led to reductions of two and four logs, respectively.</p></sec><sec><title>Conclusion</title><p>Our findings underscore the effectiveness of [<sup>225</sup>Ac]4497-IgG1 and [<sup>177</sup>Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. <italic>aureus</italic> and biofilms <italic>in vitro</italic>. This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. <italic>aureus</italic> and its biofilm.</p></sec>