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

Cynthia M. Co, Aditi Mulgaonkar, Ning Zhou, Shelby Harris, Orhan K. Öz, Liping Tang, Xiankai Sun

Research output: Contribution to journalArticlepeer-review


The increasing prevalence and severity of invasive fungal infections (IFIs), especially in immunocompromised populations, has amplified the need for rapid diagnosis of fungal pathogens. Radiotracers derived from d-amino acids (DAAs) show promise as bacterial-specific positron emission tomography (PET) imaging agents due to their preferential consumption by bacteria and largely nonutilization by hosts. Unlike mammals, fungi can utilize external DAAs including d-glutamine for their growth by rapidly upregulating DAA oxidases. Additionally, glutamine is essential for fungal nitrogen assimilation, survival, and virulence. We previously validated d-[5-11C]-glutamine (d-[5-11C]-Gln) as an efficient radiotracer targeting live bacterial soft-tissue infections. Here, we further expanded this investigation to evaluate its translational potential for PET imaging of IFIs in immunocompetent mouse models subcutaneously (SubQ) and intramuscularly (IM) infected with Candida albicans (C. albicans), using its l-isomer counterpart (l-[5-11C]-Gln) as a control. Comparative studies between pathogens showed significantly (p < 0.05) higher uptake in fungi (C. albicans and C. tropicalis) versus tested bacterial species for d-[5-11C]-Gln, suggesting that it could potentially serve as a more sensitive radiotracer for detection of fungal infections. Additionally, comparative PET imaging studies in immunocompetent infected mice demonstrated significantly higher infection-to-background ratios for d- versus l-[5-11C]-Gln in both SubQ (ratio = 1.97, p = 0.043) and IM (ratio = 1.97, p = 0.028) infections. Fungal infection imaging specificity was confirmed with no significant difference observed between localized inflammation sites versus untreated muscle background (heat-killed injection site/untreated muscle: ∼1.1). Taken together, this work demonstrates the translational potential of d-[5-11C]-Gln for noninvasive PET imaging of IFIs.

Original languageEnglish (US)
Pages (from-to)1663-1673
Number of pages11
JournalACS infectious diseases
Issue number8
StatePublished - Aug 12 2022


  • d-amino acid
  • fungal infection
  • glutamine
  • metabolic imaging
  • positron emission tomography

ASJC Scopus subject areas

  • Infectious Diseases


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