The Effects of Radioimmunotherapy and Antibiotics on Biofilm-Associated Implant Infections in a Preclinical Rat Model

Abstract

Indwelling medical implants are susceptible to developing biofilm-associated infections that are notoriously difficult to eradicate. These persistent infections often cannot be resolved with antibiotics alone and typically require surgical intervention for effective management. An alternative approach is radioimmunotherapy (RIT) which uses specific antibodies linked to radioisotopes to selectively destroy bacteria. This antimicrobial approach bypasses traditional antibiotic mechanisms, and RIT is hypothesized to enhance outcomes beyond antibiotic therapy alone. RIT bactericidal effects were studied in Wistar Han rats fitted with femoral rod implants covered by matured 3-day biofilms. The rats (six per group) were treated with either: RIT with 177Lu-labeled 4497 antibody to S. aureus teichoic wall acid (WTA) (116.6 MBq/kg), or vancomycin (88 mg/kg), or combination of RIT (116.8 MBq/kg) and vancomycin, or left untreated. To evaluate efficacy, bacterial counts were taken from the joint capsule, bone, and implant after 7 days. Uptake and biodistribution were assessed via non-invasive in vivo SPECT/CT imaging and ex vivo gamma counting. Single administration of RIT achieved a 2.7-log (99.78%) reduction of bacterial burden in the infected joint capsule, had no effect on the infected femur, and resulted in 72.5% reduction of bacterial burden on the infected implant when compared to untreated controls. RIT reduced bacterial burden and inflammation in experimental PJI with no side effects. These findings underscore the potential of RIT in the treatment of infected indwelling devices and warrant further study.