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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents



ID: 682124.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
Heterogeneity in lung (18)FDG uptake in pulmonary arterial hypertension: potential of dynamic (18)FDG positron emission tomography with kinetic analysis as a bridging biomarker for pulmonary vascular remodeling targeted treatments
Authors:Zhao, L.; Ashek, A.; Wang, L.; Fang, W.; Dabral, S.; Dubois, O.; Cupitt, J.; Pullamsetti, S. S.; Cotroneo, E.; Jones, H.; Tomasi, G.; Nguyen, Q. D.; Aboagye, E. O.; El-Bahrawy, M. A.; Barnes, G.; Howard, L. S.; Gibbs, J. S.; Gsell, W.; He, J. G.; Wilkins, M. R.
Date of Publication (YYYY-MM-DD):2013-09-10
Journal Abbrev.:Circulation
Volume:128
Issue / Number:11
Start Page:1214
End Page:1224
Audience:Not Specified
Abstract / Description:BACKGROUND: Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH. METHODS AND RESULTS: Dynamic positron emission tomography imaging with fluorine-18-labeled 2-fluoro-2-deoxyglucose ((18)FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score: 3.27+/-1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02+/-0.71; P<0.05). Further compartment analysis confirmed increased lung glucose metabolism in IPAH. Lung (18)FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patients, consistent with the recognized heterogeneity of vascular pathology in this disease. The monocrotaline rat PAH model also showed increased lung (18)FDG uptake, which was reduced along with improvements in vascular pathology after treatment with dicholoroacetate and 2 tyrosine kinase inhibitors, imatinib and sunitinib. Hyperproliferative pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expression, along with increased cellular (18)FDG uptake; both were reduced by dicholoroacetate and imatinib. CONCLUSIONS: Some patients with IPAH exhibit increased lung (18)FDG uptake. (18)FDG positron emission tomography imaging is a tool to investigate the molecular pathology of PAH and its response to treatment.
Free Keywords:Adult; Aged; Animals; Benzamides/therapeutic use; Cell Division; Dichloroacetic Acid/therapeutic use; Disease Models, Animal; Drug Monitoring; Female; Fibroblasts/drug effects/pathology; Fluorine Radioisotopes/diagnostic use/*pharmacokinetics; Fluorodeoxyglucose F18/diagnostic use/*pharmacokinetics; Gene Expression Profiling; Glycolysis/genetics; Humans; Hypertension, Pulmonary/chemically induced/drug therapy/metabolism/*radionuclide; imaging; Indoles/therapeutic use; Lung/metabolism/*radionuclide imaging; Male; Middle Aged; Monocrotaline/toxicity; Piperazines/therapeutic use; *Positron-Emission Tomography; Protein Kinase Inhibitors/therapeutic use; Pyrimidines/therapeutic use; Pyrroles/therapeutic use; Radiopharmaceuticals/diagnostic use/*pharmacokinetics; Rats; Rats, Sprague-Dawley; Young Adult
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1524-4539 (Electronic) 0009-7322 (Linking) %R 10.1161/CIRCULATIONAHA.113.004136
URL:http://www.ncbi.nlm.nih.gov/pubmed/23900048
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