title: Pulmonary elimination rate of inhaled 99mTc-sestamibi radioaerosol is delayed in healthy cigarette smokers.
abstract: BACKGROUND
  * Very little is known about the physiology of P-glycoprotein (P-gp) expression in the lungs. * Ex vivo evidence based on resected lung tissue suggests that pulmonary P-gp is upregulated by cigarette smoke, but there are no in vivo studies to date.
  
  
  CONCLUSIONS
  * The novel observation that healthy cigarette smokers have a delayed pulmonary elimination rate of inhaled (99m)Tc-sestamibi, a P-gp substrate, provides for the first time a potential method for quantifying functional pulmonary P-gp expression that may inform about drug therapy by inhalation as well as provide a non-invasive, quantitative, human biomarker for assessing P-gp modulators.
  
  
  OBJECTIVE
  To explore inhaled technetium-99m-labelled hexakis-methoxy-isobutyl isonitrile ((99m)Tc-sestamibi) for quantifying pulmonary P-glycoprotein (P-gp) expression.
  
  
  METHODS
  The elimination rate from the lungs of (99m)Tc-sestamibi was recorded scintigraphically for 30 min following inhalation as an aerosol in healthy smokers, nonsmokers and patients with lung disease.
  
  
  RESULTS
  (99m)Tc-sestamibi elimination rates [% min(-1) (SD; P vs. healthy nonsmokers)] were: healthy nonsmokers, 0.43 (0.083); healthy smokers, 0.19 (0.056; P < 0.001); chronic obstructive pulmonary disease patients, 0.26 (0.077; P < 0.001). Elimination rates in three patients with interstitial lung disease were not accelerated.
  
  
  CONCLUSIONS
  Cigarette smoke upregulates lung P-gp. (99m)Tc-sestamibi elimination in normal smokers could be used to test new P-gp modulators. The findings also have implications for inhaled drug delivery.
authors.affiliation: Department of Radiology, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Cambridge, UK.
authors.forename: Prina
authors.initials: P
authors.lastname: Ruparelia
authors.forename: Heok K
authors.initials: HK
authors.lastname: Cheow
authors.forename: John W
authors.initials: JW
authors.lastname: Evans
authors.forename: Leith
authors.initials: L
authors.lastname: Banney
authors.forename: Sonal
authors.initials: S
authors.lastname: Shankar
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Szczepura
authors.forename: Anna E
authors.initials: AE
authors.lastname: Swift
authors.forename: James R
authors.initials: JR
authors.lastname: Ballinger
authors.forename: Neil G
authors.initials: NG
authors.lastname: Hartman
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chilvers
authors.forename: A Michael
authors.initials: AM
authors.lastname: Peters
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008173:Lung Diseases, Obstructive / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012129:Respiratory Function Tests / Q000379:methods; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D017256:Technetium Tc 99m Sestamibi
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi