Document Detail


Lung ¹⁸F-fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of pulmonary arterial hypertension.
MedLine Citation:
PMID:  22246173     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Pulmonary arterial hypertension (PAH) is a proliferative arteriopathy associated with glucose transporter-1 (Glut1) up-regulation and a glycolytic shift in lung metabolism. Glycolytic metabolism can be detected with the positron emission tomography (PET) tracer (18)F-fluorodeoxyglucose (FDG).
OBJECTIVES: The precise cell type in which glycolytic abnormalities occur in PAH is unknown. Moreover, whether FDG-PET is sufficiently sensitive to monitor PAH progression and detect therapeutic regression is untested. We hypothesized that increased lung FDG-PET reflects enhanced glycolysis in vascular cells and is reversible in response to effective therapies.
METHODS: PAH was induced in Sprague-Dawley rats by monocrotaline or chronic hypoxia (10% oxygen) in combination with Sugen 5416. Monocrotaline rats were treated with oral dichloroacetate or daily imatinib injections. FDG-PET scans and pulmonary artery acceleration times were obtained weekly. The origin of the PET signal was assessed by laser capture microdissection of airway versus vascular tissue. Metabolism was measured in pulmonary artery smooth muscle cell (PASMC) cultures, using a Seahorse extracellular flux analyzer.
MEASUREMENTS AND MAIN RESULTS: Lung FDG increases 1-2 weeks after monocrotaline (when PAH is mild) and is normalized by dichloroacetate and imatinib, which both also regress medial hypertrophy. Glut1 mRNA is up-regulated in both endothelium and PASMCs, but not airway cells or macrophages. PASMCs from monocrotaline rats are hyperproliferative and display normoxic activation of hypoxia-inducible factor-1α (HIF-1α), which underlies their glycolytic phenotype.
CONCLUSIONS: HIF-1α-mediated Glut1 up-regulation in proliferating vascular cells in PAH accounts for increased lung FDG-PET uptake. FDG-PET is sensitive to mild PAH and can monitor therapeutic changes in the vasculature.
Authors:
Glenn Marsboom; Christian Wietholt; Chad R Haney; Peter T Toth; John J Ryan; Erik Morrow; Thenappan Thenappan; Peter Bache-Wiig; Lin Piao; Jonathan Paul; Chin-Tu Chen; Stephen L Archer
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-12
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  185     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-16     Completed Date:  2012-05-15     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  670-9     Citation Subset:  AIM; IM    
Affiliation:
Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Disease Progression
Fluorodeoxyglucose F18 / diagnostic use*,  pharmacokinetics
Hypertension, Pulmonary / metabolism,  physiopathology,  radionuclide imaging*
Monitoring, Physiologic / methods*
Oxygen Consumption
Positron-Emission Tomography / methods*
Pulmonary Wedge Pressure / physiology*
Radiopharmaceuticals / diagnostic use,  pharmacokinetics
Rats
Rats, Sprague-Dawley
Reproducibility of Results
Grant Support
ID/Acronym/Agency:
1RC1HL099462-01/HL/NHLBI NIH HHS; R01-HL071115/HL/NHLBI NIH HHS; S10 RR022520/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Radiopharmaceuticals; 63503-12-8/Fluorodeoxyglucose F18
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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