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A Siderophore-Antibiotic Heterodimer Imaging Agent Enables In Vivo PET Imaging of S. aureus Infections
Collin E Merrick1, Mou Chakraborty2, John M Van Wazer2
1Department of Chemistry, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130, United States.
Abstract:
Only a handful of bacterial strains are responsible for the majority of clinical infections, with Staphylococcus aureus being the single largest contributor. S. aureus infections can be very hard to confirm and localize. There is a clinical need for improved imaging technologies to detect and characterize bacterial infections allowing for prompt initiation of treatment. We generated a molecule for positron emission tomography (PET) imaging of bacterial infection by linking two clinically used small molecules, Vancomycin (Vanco) and desferrioxamine B (DFO). This siderophore-antibiotic conjugate marries the high specificity of the antibiotic for Gram-positive bacteria with the receptor targeting and chelation capabilities of the siderophore. The conjugate can be labeled with 68Ga for in vivo detection by PET. We report here the scalable synthesis of the heterodimeric probe [68Ga][Ga(DFO-PEG-Vanco)], the biochemical validation of its mechanism of action, its biodistribution, and the ability to image S. aureus infection in vivo.
Insights
A novel positron emission tomography (PET) imaging agent was developed by linking Vancomycin (Vanco) and desferrioxamine B (DFO). This agent successfully images Staphylococcus aureus infections in vivo.
Area of Science:
- Biomedical Imaging
- Infectious Diseases
- Radiochemistry
Background:
- Staphylococcus aureus is a leading cause of clinical infections.
- Current methods for detecting and localizing S. aureus infections are often challenging.
- There is a significant clinical need for advanced imaging techniques to diagnose bacterial infections promptly.
Purpose of the Study:
- To develop a novel positron emission tomography (PET) imaging agent for detecting Gram-positive bacterial infections.
- To create a molecular probe by conjugating Vancomycin (Vanco) and desferrioxamine B (DFO).
- To evaluate the efficacy of the developed probe for in vivo imaging of S. aureus.
Main Methods:
- Synthesis of a heterodimeric probe [68Ga][Ga(DFO-PEG-Vanco)] by linking Vanco and DFO.
- Biochemical validation of the probe's mechanism of action.
- Assessment of the probe's biodistribution and in vivo imaging capabilities using PET.
Main Results:
- Scalable synthesis of the [68Ga][Ga(DFO-PEG-Vanco)] probe was achieved.
- The probe demonstrated specific binding to Gram-positive bacteria via Vancomycin.
- Successful in vivo imaging of Staphylococcus aureus infection was achieved using the developed PET agent.
Conclusions:
- The novel siderophore-antibiotic conjugate is a promising PET imaging agent for bacterial infections.
- The probe allows for targeted detection and characterization of S. aureus infections.
- This technology has the potential to improve early diagnosis and treatment initiation for S. aureus infections.
