Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Abstract

Positron emission tomography is a three-dimensional imaging technique that measures physiological effects, including metabolism. 18 Fluorodeoxyglucose has been extensively used as a tracer of cellular energy metabolism in the brain and in tumour detection. As neutrophils utilise glucose as an energy source during their respiratory burst, it was hypothesised that 18 fluorodeoxyglucose uptake, by these cells, could be interpreted as a measure of neutrophil activation in cystic fibrosis (CF).Ten adult CF patients were given a bolus intravenous injection of 18 fluorodeoxyglucose, followed by a 90-min dynamic mid-lung acquisition scan. Right-lung 18 fluorodeoxyglucose uptake was assessed using a Patlak plot and values were converted to glucose utilisation. Three clinically inactive pulmonary sarcoidosis patients served as controls.From the 10 CF patients with baseline sputum neutrophils of 14610 6 cells?mL -1 who were investigated, seven were found to have sputum at a normal or slightly depressed glucose utilisation rate (mean 1.33 mmol?g Positron emission tomography (PET) is a powerful, quantitative, nuclear medicine tomographic imaging technique. PET can be used to measure physiological effects such as blood flow, metabolism, ventilation, receptor occupancy, regional dose delivery and pharmacokinetics of radiolabelled drugs [1]. It combines principles of image reconstruction from projections with the use of specific biological molecules labelled with positron-emitting radioisotopes ( 11 C, 18 F, 15 O, 13 N) allowing regional measurements of dynamic processes to be taken. 18 FDG differs from glucose by the substitution of the hydroxyl group with a fluorine atom on the second carbon of the glucose. When injected intravenously, 18 FDG rapidly diffuses into the extracellular spaces throughout the body. It is transported into living cells by the same mechanism as glucose, via the D-glucose transporter and is phosphorylated by hexokinase to fluoro-deoxyglucose-6-phosphate. The deoxy substitution at the second carbon position prevents further metabolism and the product accumulates in the cell at a rate that reflects glucose metabolism. Increased glucose consumption is assumed to lead to an increased rate of tracer uptake. The rate of accumulation of 18 FDG in tissue after intravenous injection reflects the combined transport and hexokinase activity in the cells [9].18 FDG-PET studies of the lung are still relatively few compared with the number of oncological, neurological and cardiac studies.The inflammatory process, in particular neutrophils, has been implicated in the pathogenesis of a variety of lung diseases including cystic fibrosis (CF), bronchiectasis, and chronic bronchitis. Neutrophils contribute to pulmonary destruction by production and release of cytotoxic enzymes (e.g. elastase, myeloperoxidase) and toxic oxygen metabolites [10]. Markers of inflammation in blood, bronchoalveolar lavage (BAL), sputum and lung biopsy serve as indirect measurements of inflammation, making the detection of re...

Quantifying Pulmonary Inflammation in Cystic Fibrosis with Positron Emission Tomography

“…Regardless of which method is used, our data show significant differences between the rate of [ (39). However, in a reanalysis of their data, they found that the three patients who had an elevated uptake of [ 18 F]FDG by PET also had an increased rate of decline in pulmonary function (using the same criteria of Rosenbluth and colleagues [12])-consistent with our "rapidly declining" group-whereas the rate of decline in the seven patients who had no elevation in the uptake of [ 18 F]FDG was consistent with our "stable" group (Dr. R. Labiris, personal communication).…”

PET/CT in nononcological lung diseases: current applications and future perspectives

“…Thus, the optimal therapy for CF should be able to counteract the deleterious effects of neutrophil activation without impairing host defences against infection. CHEN and SCHUSTER [75] showed significant differences between the rate of FDG uptake by the lungs of 20 adult patients with CF versus seven adult normal volunteers and, similarly to LABIRIS et al [76], suggested that FDG-PET may discriminate patients with more rapidly declining lung function. In particular, they found that patients with CF and higher rates of decline in pulmonary function have higher numbers of neutrophils in BAL and higher PET-measured rates of FDG uptake.…”

Quantification of Lung PET Images: Challenges and Opportunities

“…Inflammation characterizes several lung diseases, including pneumonia, cystic fibrosis, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), asthma, and interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF), among others (7,8,10,11,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Because ARDS, COPD, and IPF can cause significant variability in the amounts of air, blood, and water in the lungs (Fig.…”