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

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.

doi:10.3390/ijms24054374

Open AccessArticle

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

by

Bruce van Dijk

^1,*,

J. Fred F. Hooning van Duyvenbode

¹,

Lisanne de Vor

²,

F. Ruben H. A. Nurmohamed

¹,

Marnix G. E. H. Lam

³,

Alex J. Poot

³,

Ruud M. Ramakers

^4,5,6,

Sofia Koustoulidou

^4,6,

Freek J. Beekman

^4,5,6,

Jos van Strijp

²,

Suzan H. M. Rooijakkers

²,

Ekaterina Dadachova

⁷,

H. Charles Vogely

¹

,

Harrie Weinans

^1,8 and

Bart C. H. van der Wal

¹

Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands

²

Department of Medical Microbiology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands

³

Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands

⁴

MILabs B.V., 3584 CX Utrecht, The Netherlands

⁵

Department of Radiation Science and Technology, Delft University of Technology, 2628 CD Delft, The Netherlands

⁶

Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, 3584 CX Utrecht, The Netherlands

⁷

College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada

⁸

Department of BioMechanical Engineering, Delft University of Technology, 2628 CD Delft, The Netherlands

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2023, 24(5), 4374; https://doi.org/10.3390/ijms24054374

Submission received: 26 December 2022 / Revised: 6 February 2023 / Accepted: 16 February 2023 / Published: 22 February 2023

(This article belongs to the Special Issue Targeted Radionuclide Therapy of Cancer and Infections)

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Abstract

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 ¹¹¹In-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 ¹¹¹In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm³ at 24 h to 9.22 %ID/cm³ at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm³, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm³ at 120 h. The effective half-life of ¹¹¹In-4497 mAbs was determined to be 59 h. In conclusion, ¹¹¹In-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.

Keywords: antibody; biodistribution; infection; mice; periprosthetic joint infection; radioimmunotherapy; theranostics; radiolabeling; S. aureus; SPECT

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MDPI and ACS Style

van Dijk, B.; Hooning van Duyvenbode, J.F.F.; de Vor, L.; Nurmohamed, F.R.H.A.; Lam, M.G.E.H.; Poot, A.J.; Ramakers, R.M.; Koustoulidou, S.; Beekman, F.J.; van Strijp, J.; et al. Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo. Int. J. Mol. Sci. 2023, 24, 4374. https://doi.org/10.3390/ijms24054374

AMA Style

van Dijk B, Hooning van Duyvenbode JFF, de Vor L, Nurmohamed FRHA, Lam MGEH, Poot AJ, Ramakers RM, Koustoulidou S, Beekman FJ, van Strijp J, et al. Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo. International Journal of Molecular Sciences. 2023; 24(5):4374. https://doi.org/10.3390/ijms24054374

Chicago/Turabian Style

van Dijk, Bruce, J. Fred F. Hooning van Duyvenbode, Lisanne de Vor, F. Ruben H. A. Nurmohamed, Marnix G. E. H. Lam, Alex J. Poot, Ruud M. Ramakers, Sofia Koustoulidou, Freek J. Beekman, Jos van Strijp, and et al. 2023. "Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo" International Journal of Molecular Sciences 24, no. 5: 4374. https://doi.org/10.3390/ijms24054374

APA Style

van Dijk, B., Hooning van Duyvenbode, J. F. F., de Vor, L., Nurmohamed, F. R. H. A., Lam, M. G. E. H., Poot, A. J., Ramakers, R. M., Koustoulidou, S., Beekman, F. J., van Strijp, J., Rooijakkers, S. H. M., Dadachova, E., Vogely, H. C., Weinans, H., & van der Wal, B. C. H. (2023). Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo. International Journal of Molecular Sciences, 24(5), 4374. https://doi.org/10.3390/ijms24054374

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

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