title: Lung ¹⁸F-fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of pulmonary arterial hypertension.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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.
  
  
  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.affiliation: Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Marsboom
authors.forename: Christian
authors.initials: C
authors.lastname: Wietholt
authors.forename: Chad R
authors.initials: CR
authors.lastname: Haney
authors.forename: Peter T
authors.initials: PT
authors.lastname: Toth
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.forename: Erik
authors.initials: E
authors.lastname: Morrow
authors.forename: Thenappan
authors.initials: T
authors.lastname: Thenappan
authors.forename: Peter
authors.initials: P
authors.lastname: Bache-Wiig
authors.forename: Lin
authors.initials: L
authors.lastname: Piao
authors.forename: Jonathan
authors.initials: J
authors.lastname: Paul
authors.forename: Chin-Tu
authors.initials: CT
authors.lastname: Chen
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Archer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D065627:Familial Primary Pulmonary Hypertension; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D008991:Monitoring, Physiologic / Q000379:methods*; D010101:Oxygen Consumption; D049268:Positron-Emission Tomography / Q000379:methods*; D011669:Pulmonary Wedge Pressure / Q000502:physiology*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18