Pathogen-Specific PET Imaging of Pulmonary Infection Using [¹⁸F]Fluoromannitol

Pneumonia remains a leading cause of global morbidity and mortality, with diagnostic uncertainty frequently complicating clinical management, particularly in patients with chronic lung disease, immunocompromise, or healthcare-associated infections. Conventional imaging modalities and microbiologic testing lack specificity for distinguishing bacterial pneumonia from viral infection, sterile inflammation, or noninfectious lung disease, often resulting in empiric antibiotic overuse and delayed alternative therapies. In this study, we evaluated [¹⁸F]-fluoromannitol, a pathogen-specific Positron Emission Tomography (PET) tracer, in well-established murine models of pulmonary infection caused by Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. Compared with controls, including heat-killed bacterial pneumonitis, influenza A virus-induced pneumonia, and noninfectious Poly-(I:C) induced pneumonia. [¹⁸F]-fluoromannitol PET enabled robust, rapid, and anatomically localized detection of active bacterial pneumonia, with tracer uptake correlating with bacterial burden and disease progression. These findings demonstrate that [¹⁸F]-fluoromannitol PET can noninvasively distinguish bacterial lung infection from viral and noninfectious etiologies. By directly targeting bacterial metabolism rather than host inflammation, this approach offers a promising strategy to improve etiologic classification of lower respiratory tract infections and support antimicrobial stewardship.