PET imaging of regional¹⁸F-FDG uptake and lung function after cigarette smoke inhalation

Cigarette smoke is thought to promote local lung inflammation that leads to lung dysfunction. Lung neutrophilic inflammation is known to result in increased pulmonary uptake of ¹⁸F-FDG. Using a sheep model of localized exposure to cigarette smoke, in this study we tested whether PET-imaged changes in regional intrapulmonary distribution of ¹⁸F-FDG uptake are related to changes in regional lung function as assessed with the infused ¹³NN-saline method. Methods: Five anesthetized, mechanically ventilated sheep were exposed to unilateral inhalation of smoke from 10 tobacco cigarettes while the contralateral lung was ventilated with smoke-free gas. Two hours after the exposure, regional gas content was measured from a transmission scan; regional ventilation, perfusion, and shunt were measured from the kinetics of ¹³NN-saline; and regional ¹⁸F-FDG influx constant (K_i) was calculated with the Patlak algorithm applied at a voxel-by-voxel level. Results: K_i was higher and more heterogeneous in the smoke-exposed lungs than in the control lungs (P < 0.05). Spatial heterogeneity of K_i and impairment in regional lung function were quite variable among animals despite similar levels of smoke exposure. However, increases in mean K_i correlated linearly with its spatial heterogeneity (Spearman correlation, r_s = 0.94), and the highest levels of regional K_i in smoke-exposed lungs and control lungs correlated with regional shunt fraction (r_s = 0.78). Also, the heterogeneity of the ventilation-perfusion (V̇/Q̇) distribution of the smoke-exposed lungs was 10 times greater than that of the control lungs but correlated strongly with that of the control lungs (r = 0.998). Conclusion: Substantial interanimal variability and spatial heterogeneity in lung function and ¹⁸F-FDG uptake seem to characterize the response to smoke exposure. The highest levels of local ¹⁸F-FDG uptake were associated with differences in V̇/Q̇ matching and shunt fraction among animals. The data also suggest that preexisting heterogeneity in V̇/Q̇ could have been responsible for the large interanimal variability by affecting the heterogeneity and strength of the acute response to smoke inhalation.