title: Increased uptake of 111In-octreotide in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is characterized by an uncontrolled accumulation and activation of lung fibroblasts. A modulation of fibroblast activation has been observed in various systems with octreotide, a synthetic somatostatin analog with strong affinity for the somatostatin receptor subtype 2 (sst2). One aim of our study was to evaluate the expression of somatostatin receptors in the lungs of patients with IPF. A second aim was to evaluate the relationship between 111In-octreotide uptake and the effect of pulmonary fibrosis as assessed by lung function tests and parameters and by radiologic findings.
  
  
  METHODS
  We investigated 11 patients with IPF, 6 patients with pulmonary fibrosis associated with systemic sclerosis (SSc), and 19 patients with disease not of the lung (control patients). The expression of somatostatin receptors was evaluated in vivo using 111In-octreotide scintigraphy. We evaluated the relationship between 111In-octreotide uptake and the activity of pulmonary fibrosis as assessed by lung function tests, bronchoalveolar lavage (BAL) cellularity, and high-resolution CT (HRCT) of the chest. Planar images and thoracic SPECT (24 h) were performed after injection of 222 MBq of 111In-octreotide. Lung uptake was quantified using the lung-to-background ratio (L/B). In addition, the expression of sst2 was evaluated in vitro, in frozen lung-tissue samples using autoradiography, and in human cultures of lung fibroblasts using a ligand-binding assay.
  
  
  RESULTS
  Compared with lung uptake in control patients (median L/B, 1.25; range, 1.14-1.49), lung uptake was increased in all 11 IPF patients (median L/B, 2.63; range, 1.59-3.13; P < 0.001) and in 4 of 6 SSc patients (median L/B, 1.68; range, 1.42-2.16). The L/B was lower in SSc patients than in IPF patients (P = 0.011). Increased uptake correlated with the alteration of lung function (carbon monoxide diffusing capacity [rho = -0.655; P = 0.038], diffusing capacity for carbon monoxide and alveolar volume ratio [rho = -0.627; P = 0.047], vital capacity [rho = -0.609; P = 0.054], and total lung capacity [rho = -0.598; P = 0.058]) and with the intensity of alveolitis (total BAL cellularity [rho = 0.756; P = 0.045], neutrophil counts [rho = 0.738; P = 0.05]), and HRCT fibrosis score (rho = 0.673; P = 0.007). Autoradiography suggested that vascular structures were a prominent binding site. Lung fibroblasts expressed somatostatin receptors in vitro as measured by binding assay.
  
  
  CONCLUSIONS
  Our preliminary results identified an increased expression of sst2 in (mainly idiopathic) pulmonary fibrosis. Lung uptake correlates with the alteration of lung function and with the intensity of alveolitis.
authors.affiliation: Department of Nuclear Medicine, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France. rachida.lebtahi@bch.aphp.fr
authors.forename: Rachida
authors.initials: R
authors.lastname: Lebtahi
authors.forename: Severine
authors.initials: S
authors.lastname: Moreau
authors.forename: Sylvain
authors.initials: S
authors.lastname: Marchand-Adam
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Debray
authors.forename: Michel
authors.initials: M
authors.lastname: Brauner
authors.forename: Paul
authors.initials: P
authors.lastname: Soler
authors.forename: Joëlle
authors.initials: J
authors.lastname: Marchal
authors.forename: Olivier
authors.initials: O
authors.lastname: Raguin
authors.forename: Anne
authors.initials: A
authors.lastname: Gruaz-Guyon
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Reubi
authors.forename: Dominique
authors.initials: D
authors.lastname: Le Guludec
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D017481:Receptors, Somatostatin / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007205:Indium Radioisotopes; D017481:Receptors, Somatostatin; D015282:Octreotide