Radioimmunotherapy combating biofilm-associated infection in vitro

Area of Science:

• Orthopedic Surgery
• Radiopharmaceutical Therapy
• Infectious Diseases

Background:

• Prosthetic joint infections are a significant challenge in orthopedic surgery, associated with high morbidity and mortality.
• Staphylococcus aureus and its biofilms complicate treatment outcomes.
• Novel therapeutic strategies are needed to address these challenging infections.

Purpose of the Study:

• To evaluate radioimmunotherapy as a potential treatment for biofilm-associated Staphylococcus aureus infections.
• To investigate the efficacy of monoclonal antibodies targeting S. aureus wall teichoic acids conjugated with radionuclides.

Main Methods:

• Monoclonal antibodies (4497-IgG1) targeting S. aureus wall teichoic acids were conjugated with actinium-225 (225Ac) and lutetium-177 (177Lu) using DOTA.
• In vitro susceptibility of S. aureus planktonic cultures and biofilms to radioimmunotherapy was assessed.
• Bacterial viability and metabolic activity were measured using colony-forming unit enumeration and xylenol tetrazolium assays.

Main Results:

• Both [225Ac]4497-IgG1 and [177Lu]4497-IgG1 demonstrated dose-dependent reductions in S. aureus viability and biofilm formation over 96 hours.
• A four-log reduction in planktonic S. aureus was observed with specific doses of both radioimmunoconjugates.
• Significant log reductions in biofilm bacterial counts were achieved, with [177Lu]4497-IgG1 showing a four-log reduction.

Conclusions:

• Radioimmunotherapy with [225Ac]4497-IgG1 and [177Lu]4497-IgG1 exhibits potent in vitro bactericidal effects against S. aureus and its biofilms.
• This approach offers a promising targeted strategy for managing S. aureus infections, particularly those involving biofilms.