FDG-PET imaging of pulmonary inflammation in healthy volunteers after airway instillation of endotoxin

Recent studies indicate that a focal, limited, inflammatory response can be safely elicited after direct bronchial instillation of small doses of endotoxin into a single lung segment. Because the radiotracer [F-18] fluorodeoxyglucose ([F-18]FDG) is taken up at accelerated rates within inflamed tissues, we hypothesized that we could detect and quantify this regional inflammatory response with positron emission tomography ( PET). We imaged 18 normal volunteers in a dose-escalation study with 3 endotoxin dosing groups (n = 6 in each group): 1 ng/ kg, 2 ng/ kg, and 4 ng/ kg. Endotoxin was instilled by bronchoscopy into a segment of the right middle lobe, with imaging performed similar to 24 h later, followed by bronchoalveolar lavage (BAL). A "subtraction imaging analysis" was performed in the highest dose cohort to identify the area of inflammation, using the preendotoxin scan as a baseline. BAL neutrophil counts were significantly higher in the highest dose group compared with the other two groups (1,413 +/- 625 vs. 511 +/- 396 and 395 +/- 400 cells/ mm(3); P < 0.05). Autoradiography performed on cells harvested by BAL showed specific [H-3] deoxyglucose ([H-3]DG) uptake limited to neutrophils. In vitro [H-3] DG uptake in BAL neutrophils in the 4 ng/ kg dose group ( but not in the 2 ng/ kg group) was statistically greater than in peripheral blood neutrophils obtained before endotoxin instillation. The rate of [F-18] FDG uptake was greatest in the 4 ng/ kg group, with a consistent, statistically significant increase in the rate of uptake after endotoxin instillation compared with baseline. We conclude that the inflammatory response to low-dose endotoxin in a single lung segment can be visualized and quantified by imaging with FDG-PET.