Radioimmunotherapy combating biofilm-associated infection in vitro.

BACKGROUND: 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 Staphylococcus aureus (S. aureus) further complicates the scenario. OBJECTIVE: To investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections. METHODS: Our methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on S. aureus and its biofilm. These antibodies were linked with radionuclides actinium-225 ((225)Ac) and lutetium-177 ((177)Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of S. aureus and its biofilm to radioimmunotherapy in vitro, assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays. RESULTS: Both [(225)Ac]4497-IgG1 and [(177)Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in S. aureus 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 [(225)Ac]4497-IgG1 and [(177)Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [(225)Ac]4497-IgG1 and 14.8 Mbq [(177)Lu]4497-IgG1 led to reductions of two and four logs, respectively. CONCLUSION: Our findings underscore the effectiveness of [(225)Ac]4497-IgG1 and [(177)Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. aureus and biofilms in vitro. This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. aureus and its biofilm.