PET Imaging of Active Invasive Fungal Infections with d-[5-¹¹C]-Glutamine

Area of Science:

• Medical Imaging
• Nuclear Medicine
• Infectious Diseases

Background:

• Invasive fungal infections (IFIs) are a growing concern, particularly in immunocompromised individuals.
• Rapid and accurate diagnosis of IFIs is crucial for effective treatment.
• Radiotracers derived from d-amino acids (DAAs) show potential for pathogen-specific imaging.

Purpose of the Study:

• To evaluate the translational potential of d-[5-¹¹C]-glutamine (d-[5-¹¹C]-Gln) for positron emission tomography (PET) imaging of invasive fungal infections (IFIs).
• To compare the efficacy of d-[5-¹¹C]-Gln against its l-isomer control for imaging fungal infections in mouse models.

Main Methods:

• Developed and validated d-[5-¹¹C]-glutamine (d-[5-¹¹C]-Gln) as a PET imaging radiotracer.
• Infected immunocompetent mice with *Candida albicans* subcutaneously (SubQ) and intramuscularly (IM).
• Utilized l-[5-¹¹C]-Gln as a control and compared uptake in fungal versus bacterial infections.

Main Results:

• d-[5-¹¹C]-Gln showed significantly higher uptake in fungi (*C. albicans*, *C. tropicalis*) compared to tested bacterial species.
• PET imaging in infected mice revealed significantly higher infection-to-background ratios for d-[5-¹¹C]-Gln versus l-[5-¹¹C]-Gln in both SubQ and IM models.
• Imaging specificity was confirmed, with no significant uptake difference between inflammation sites and background muscle.

Conclusions:

• d-[5-¹¹C]-Gln demonstrates translational potential for noninvasive PET imaging of invasive fungal infections.
• This radiotracer shows promise for sensitive and specific detection of fungal pathogens.
• Further research may lead to improved diagnostic tools for IFIs.