Distributable, metabolic PET reporting of tuberculosis

Area of Science:

• Biomedical Imaging
• Radiochemistry
• Infectious Diseases

Background:

• Tuberculosis (TB) presents a significant global health challenge, marked by lengthy treatment and difficult disease monitoring.
• Current diagnostic methods, primarily sputum culture, have limitations in detecting TB and assessing treatment efficacy.
• Existing imaging agents like [18F]FDG lack specificity for Mycobacterium tuberculosis (Mtb), hindering direct correlation with pathogen viability.

Purpose of the Study:

• To develop and validate a novel positron-emitting tracer for specific in vivo imaging of Mycobacterium tuberculosis (Mtb).
• To assess the utility of the tracer in diverse disease models for monitoring TB lesions and treatment response.
• To establish a practical and scalable method for the synthesis of the tracer from a widely available precursor.

Main Methods:

• Synthesis of 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT), a mimic of Mtb's disaccharide trehalose.
• In vivo imaging studies using [18F]FDT in various TB disease models, including non-human primates.
• Evaluation of a direct, enzyme-catalyzed radiochemical synthesis of [18F]FDT from [18F]FDG.

Main Results:

• [18F]FDT demonstrated mechanism-based reporter activity, specifically imaging Mtb via Mtb-mediated trehalose processing.
• Successful imaging of TB-associated lesions and monitoring of treatment effects were achieved in diverse preclinical models.
• A pyrogen-free, direct enzyme-catalyzed synthesis enabled efficient production of [18F]FDT from [18F]FDG.

Conclusions:

• [18F]FDT is a bacterium-selective PET tracer that specifically targets Mtb, offering a significant advancement over current imaging methods.
• The developed synthesis method allows for the production of clinical-grade [18F]FDT from the widely available [18F]FDG.
• This technology has the potential to democratize access to TB-specific PET imaging globally, aiding diagnosis and treatment management.