Evaluating the Targeting of a IStaphylococcus-aureus/I-Infected Implant with a Radiolabeled Antibody In Vivo

• Published in: International journal of molecular sciences 2023-02, Vol.24 (5)
• Main Authors: van Dijk, Bruce, Hooning van Duyvenbode, J. Fred F, de Vor, Lisanne, Nurmohamed, F. Ruben H. A, Lam, Marnix G. E. H, Poot, Alex J, Ramakers, Ruud M, Koustoulidou, Sofia, Beekman, Freek J, van Strijp, Jos, Rooijakkers, Suzan H. M, Dadachova, Ekaterina, Vogely, H. Charles, Weinans, Harrie, van der Wal, Bart C. H
• Format: Article
• Language: English
• Subjects: Drug delivery systems; Drugs; Ethylenediaminetetraacetic acid; Evaluation; Health aspects; Implants, Artificial; Infection; Methicillin; Palivizumab; Prosthesis; Staphylococcus aureus; Staphylococcus aureus infections; Vehicles
• ISSN: 1422-0067
• DOI: 10.3390/ijms24054374

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 [sup.111]In-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 [sup.111]In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm[sup.3] at 24 h to 9.22 %ID/cm[sup.3] at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm[sup.3], whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm[sup.3] at 120 h. The effective half-life of [sup.111]In-4497 mAbs was determined to be 59 h. In conclusion, [sup.111]In-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.