Noninvasive optical and nuclear imaging of Staphylococcus-specific infection with a human monoclonal antibody-based probe

Virulence

Nicholas M. Bernthal¹  Kevin P. Francis¹  Julie E. Pickett²  John M. Thompson²  Roger V. Ortines²  Carly A. Dillen²  Alyssa G. Ashbaugh²  Lloyd S. Miller²  Daniel L. J. Thorek²  Gooitzen M. van Dam³  Francisco Romero Pastrana⁴  Jan Maarten van Dijl⁴  Girbe Buist⁴  Matthijs D. Linssen⁴  Marleen van Oosten⁴  Hedzer Hoekstra⁴  Marjolein Heuker⁴ 

[1] David Geffen School of Medicine at the University of California, Los Angeles Medical Center;Johns Hopkins University School of Medicine;Nuclear Medicine and Molecular Imaging and Intensive Care, University of Groningen, University Medical Center Groningen;University of Groningen, University Medical Center Groningen;

关键词: human monoclonal antibody;    immunodominant staphylococcal antigen A;    IsaA;    PET;    89Zr;    Staphylococcus aureus;   

DOI  :  10.1080/21505594.2017.1403004

来源: DOAJ

【 摘 要 】

Staphylococcus aureus infections are a major threat in healthcare, requiring adequate early-stage diagnosis and treatment. This calls for novel diagnostic tools that allow noninvasive in vivo detection of staphylococci. Here we performed a preclinical study to investigate a novel fully-human monoclonal antibody 1D9 that specifically targets the immunodominant staphylococcal antigen A (IsaA). We show that 1D9 binds invariantly to S. aureus cells and may further target other staphylococcal species. Importantly, using a human post-mortem implant model and an in vivo murine skin infection model, preclinical feasibility was demonstrated for 1D9 labeled with the near-infrared fluorophore IRDye800CW to be applied for direct optical imaging of in vivo S. aureus infections. Additionally, 89Zirconium-labeled 1D9 could be used for positron emission tomography imaging of an in vivo S. aureus thigh infection model. Our findings pave the way towards clinical implementation of targeted imaging of staphylococcal infections using the human monoclonal antibody 1D9.

【 授权许可】

Unknown