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 (²²⁵Ac) and lutetium-177 (¹⁷⁷Lu) 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 [²²⁵Ac]4497-IgG1 and [¹⁷⁷Lu]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 [²²⁵Ac]4497-IgG1 and [¹⁷⁷Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [²²⁵Ac]4497-IgG1 and 14.8 Mbq [¹⁷⁷Lu]4497-IgG1 led to reductions of two and four logs, respectively. Conclusion: Our findings underscore the effectiveness of [²²⁵Ac]4497-IgG1 and [¹⁷⁷Lu]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.

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A”-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the ¹¹¹In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the ¹¹¹In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm³ at 24 h to 9.22 %ID/cm³ at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm³, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm³ at 120 h. The effective half-life of ¹¹¹In-4497 mAbs was determined to be 59 h. In conclusion, ¹¹¹In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm.