Validation of 2-¹⁸F-Fluorodeoxysorbitol as a Potential Radiopharmaceutical for Imaging Bacterial Infection in the Lung.

Abstract

2-¹⁸F-fluorodeoxysorbitol (¹⁸F-FDS) has been shown to be a promising agent with high selectivity and sensitivity in imaging bacterial infection. The objective of our study was to validate ¹⁸F-FDS as a potential radiopharmaceutical for imaging bacterial infection longitudinally in the lung. <b>Methods:</b> Albino C57 female mice were intratracheally inoculated with either live or dead <i>Klebsiella pneumoniae</i> to induce either lung infection or lung inflammation. One group of mice was imaged to monitor disease progression. PET/CT was performed on days 0, 1, 2, and 3 after inoculation using either ¹⁸F-FDS or ¹⁸F-FDG (<i>n</i> = 12 for each tracer). The other group was first screened by bioluminescent imaging (BLI) to select only mice with visible infection (region of interest > 10⁸ ph/s) for PET/CT imaging with ¹⁸F-FDS (<i>n</i> = 12). For the inflammation group, 5 mice each were imaged with PET/CT using either ¹⁸F-FDS or ¹⁸F-FDG from days 1 to 4 after inoculation. <b>Results:</b> For studies of disease progression, BLI showed noticeable lung infection on day 2 after inoculation and significantly greater infection on day 3. Baseline imaging before inoculation showed no focal areas of lung consolidation on CT and low uptake in the lung for both PET radiotracers. On day 2, an area of lung consolidation was identified on CT, with a corresponding 2.5-fold increase over baseline for both PET radiotracers. On day 3, widespread areas of patchy lung consolidation were found on CT, with a drastic increase in uptake for both ¹⁸F-FDS and ¹⁸F-FDG (9.2 and 3.9). PET and BLI studies showed a marginal correlation between ¹⁸F-FDG uptake and colony-forming units (<i>r</i> = 0.63) but a much better correlation for ¹⁸F-FDS (<i>r</i> = 0.85). The uptake ratio of infected lung over inflamed lung was 8.5 and 1.7 for ¹⁸F-FDS and ¹⁸F-FDG on day 3. <b>Conclusion:</b> Uptake of both ¹⁸F-FDS and ¹⁸F-FDG in infected lung could be used to track the degree of bacterial infection measured by BLI, with a minimum detection limit of 10⁷ bacteria. ¹⁸F-FDS, however, is more specific than ¹⁸F-FDG in differentiating <i>K. pneumoniae</i> lung infection from lung inflammation.