Background: Early postoperative implant infections are difficult to diagnose due to overlapping symptoms with inflammation. However, prompt surgical intervention for an implant infection can prevent the need for repeated surgeries and improve the overall success of the treatment and preserving the implant. The primary objective of this study was to assess the sensitivity and specificity of a novel immuno-PET radiotracer for detecting Staphylococcus aureus bacteria and their biofilms in a preclinical rat model. Results: An antibody against wall teichoic acid a common surface component of S. aureus, was labeled with Zirconium-89- as the PET tracer. Wistar Han rats underwent surgery with a S. aureus-related biofilm-infected femoral implant on one side and a sterile femoral implant on the contralateral side. The diagnostic efficacy of this imaging modality was compared with clinically established nuclear imaging techniques for implant infections, including [^99mTc]Tc-MDP SPECT/CT, [¹⁸F]FDG PET/CT, and [¹⁸F]NaF PET/CT. Furthermore, co-injection of unlabeled (“cold”) antibodies was performed to evaluate their impact on biodistribution. All animals with a biofilm-associated femoral implant infection showed significantly higher uptake of the novel ImmunoPET tracer in the infected side compared to the sterile side throughout the 13-day postoperative study duration. A dose-dependent increase in tracer accumulation was observed with co-injection of cold antibody, suggesting its potential to improve biodistribution. Conclusions: ImmunoPET with Zirconium-89-labeled antibodies specific for wall teichoic acid antigen demonstrates sensitive and specific diagnostic capabilities compared to conventional nuclear imaging modalities, offering a promising tool for early detection of postoperative chronic low-grade infections and septic implant loosening.

Background: the primary challenge with implant infections is the formation of biofilm, which harbors dormant bacteria that reduce the effectiveness of antibiotics and amplify antibiotic resistance, exacerbating the global antimicrobial resistance crisis. A potential novel treatment strategy is radioimmunotherapy, which uses antibodies linked to radioisotopes to deliver targeted radiation to the bacteria and biofilm. We describe the first in vivo use of targeted radiation therapy, employing Actinium-225 (α-radiation) and Lutetium-177 (β-radiation) labeled antibodies to treat a Staphylococcus aureus biofilm-associated intramedullary implant infection. Untargeted radiation in the form of unbound radionuclide treatment was also evaluated. Methods: to assess therapeutic efficacy, bacterial counts were performed on implant and surrounding bone after seven days of follow-up. Biodistribution was evaluated using SPECT/CT and ex vivo gamma counting. Results: radioimmunotherapy using an antibody against wall teichoic acid which was labeled with Actinium-225 and Lutetium-177 achieved bacterial reductions between 45% and 93% on the implant and surrounding bone. Surprisingly, a similar antimicrobial effect was observed with unbound Actinium-225 treatment reducing the bacterial load by 80% on the implant and 98% in the surrounding bone. Indications of maximum tolerated dose (MTD) with Lutetium-177 labeled antibodies were observed through hepatic and renal function evaluations. Conclusions: These results should be interpreted in the context of the study’s constraints, particularly the limited animal sample size. Nonetheless, the results suggest that in vivo applied radiation may help reduce a biofilm-associated infection at the implant site as well as in the surrounding bone. These findings encourage further investigation into the use of targeted and non-targeted radiation, potentially combined with antibiotics, to develop effective strategies for eradicating biofilm-associated implant infections.