Distributable, Metabolic PET Reporting of Tuberculosis

Area of Science:

• Biomedical Imaging
• Radiochemistry
• Infectious Diseases

Background:

• Tuberculosis (TB) diagnosis and monitoring are challenged by lengthy treatment and limited detection methods like sputum culture.
• Current imaging agents like [18F]FDG lack specificity for Mycobacterium tuberculosis (Mtb) and do not reflect pathogen viability.
• There is a critical need for a specific, non-invasive diagnostic tool for TB.

Approach:

• Developed 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT), a positron-emitting mimic of the Mtb disaccharide trehalose.
• Utilized [18F]FDT as a mechanism-based enzyme reporter for in vivo imaging of Mtb.
• Demonstrated successful imaging of Mtb lesions and treatment effects in diverse disease models, including non-human primates.

Key Points:

• [18F]FDT leverages Mtb-specific trehalose processing for targeted imaging of bacterial lesions.
• A direct, enzyme-catalyzed synthesis produces pyrogen-free [18F]FDT from readily available [18F]FDG.
• Pre-clinical validation establishes [18F]FDT as a promising bacterium-specific diagnostic candidate.

Conclusions:

• [18F]FDT enables specific imaging of TB lesions and monitoring of treatment response.
• The synthesis method allows for accessible production of clinical-grade [18F]FDT from [18F]FDG.
• This technology has the potential to democratize access to a TB-specific PET tracer globally.