Evaluating the Targeting of a Staphylococcus-aureus -Infected Implant with a Radiolabeled Antibody In Vivo.

Autor: van Dijk B; Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., Hooning van Duyvenbode JFF; Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., de Vor L; Department of Medical Microbiology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands., Nurmohamed FRHA; Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., Lam MGEH; Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., Poot AJ; Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., Ramakers RM; MILabs B.V., 3584 CX Utrecht, The Netherlands.; Department of Radiation Science and Technology, Delft University of Technology, 2628 CD Delft, The Netherlands.; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, 3584 CX Utrecht, The Netherlands., Koustoulidou S; MILabs B.V., 3584 CX Utrecht, The Netherlands.; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, 3584 CX Utrecht, The Netherlands., Beekman FJ; MILabs B.V., 3584 CX Utrecht, The Netherlands.; Department of Radiation Science and Technology, Delft University of Technology, 2628 CD Delft, The Netherlands.; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, 3584 CX Utrecht, The Netherlands., van Strijp J; Department of Medical Microbiology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands., Rooijakkers SHM; Department of Medical Microbiology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands., Dadachova E; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada., Vogely HC; Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., Weinans H; Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.; Department of BioMechanical Engineering, Delft University of Technology, 2628 CD Delft, The Netherlands., van der Wal BCH; Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Feb 22; Vol. 24 (5). Date of Electronic Publication: 2023 Feb 22.
DOI: 10.3390/ijms24054374
Abstrakt: 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 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 111 In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm 3 at 24 h to 9.22 %ID/cm 3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm 3 , whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm 3 at 120 h. The effective half-life of 111 In-4497 mAbs was determined to be 59 h. In conclusion, 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.
Competing Interests: Ruud M. Ramakers has stock appreciation rights at MILabs B.V. Freek J. Beekman is a shareholder at MILabs B.V. The other authors declare that no competing interests exist.
Databáze: MEDLINE
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