ImmunoPET with Zirconium-89 specifically detects postoperative biofilm-associated implant infections

Abstract

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.