Validation of Lung [¹⁸F]FDG Uptake as a Quantitative PET Biomarker for Influenza-Associated Pulmonary Inflammation

Influenza (flu) is a respiratory illness caused by lung infection with influenza viruses. This study establishes lung [¹⁸F]FDG uptake by PET/CT as an accurate measure of lung inflammation associated with influenza A virus (IAV) H1N1 infection.

Immunocompetent BALB/c mice were infected with a highly lethal dose of influenza A virus (PR8 strain) and intravenously injected with [¹⁸F]FDG. Ex vivo tissue biodistribution was assessed by gamma counting, while in vivo tissue biodistribution was analyzed by VOI analysis of PET/CT images. Disease severity was also investigated by VOI measurements of high-resolution lung CT images. Infection and inflammation were confirmed by immunohistochemical staining; while viral replication and expression of inflammatory proteins (cytokines and chemokines) were measured in lung tissues by qRT-PCR and multiplex ELISA, respectively.

Ex vivo tissue biodistribution of [¹⁸F]FDG revealed that the lungs were the only relevant imaging target in influenza-infected mice. Lung [¹⁸F]FDG uptake on PET/CT images increased with disease severity and exhibited 1.53-fold increase on day 1 and up to 2.63-fold increase on day 6 post-infection compared to pre-infection levels. Lung uptake correlated with the increased production of pro-inflammatory proteins associated with influenza infection.

Lung [¹⁸F]FDG uptake on PET images is a non-invasive molecular biomarker of influenza-A virus-induced lung inflammation and disease, effectively distinguishing infected from non-infected lungs as early as day 1 post-infection.