title: Inhalation scintigraphy with iodine-123-labeled interferon gamma-1b: pulmonary deposition and dose escalation study in healthy volunteers.
abstract: Recent studies have suggested that recombinant interferon gamma (IFNg) may be useful in the treatment of various respiratory diseases, such as chronic inflammatory disease. This study was undertaken to investigate the dose response of escalating doses of inhaled 123I-labeled IFNg (123I-IFNg) and its safety, biodistribution and radiation absorbed doses in healthy volunteers.
  
  
  METHODS
  IFNg was labeled with 123I to produce a specific activity of 1800 MBq/mg of IFNg. The biological activities of 123I-IFNg, nebulized 123I-IFNg and unlabeled IFNg were evaluated in various functional in vitro tests. Ten healthy volunteers were enrolled in the in vivo dose escalation study (180 MBq of 123I-IFNg diluted with 0.1-2 mg of INFg). Inhalation scintigraphy, using a Pari-Master nebulizer, was performed for up to 37 min, during which dynamic posterior images of the lungs were obtained. Whole-body scanning was performed at various time points up to 24 hr postinjection, for biodistribution and dosimetry purposes. Blood, urine and feces were also collected over this 24-hr period. Lung perfusion scintigraphy with 99mTc-microspheres was performed at the end of the study for attenuation correction.
  
  
  RESULTS
  Inhaled nebulized IFNg showed a uniform deposition pattern in the lungs with deposition ratios of 0.74 (central-to-peripheral) and 0.78 (upper-to-lower). The lung deposition of IFNg was time-dependent, with a deposition half-time between 1 and 5 min. Despite a large interindividual variation, the total lung deposition was proportional to the nebulizer charge and was 53 +/- 12% of the inhaled dose and 19 +/- 7% of the initial nebulizer charge (between 0.1 and 2 mg of IFNg). The biological half-life in the lung could be fitted to a biexponential function, with resultant half-lives of 1 and 11 hr. Blood activity was maximal at 3.5 hr after inhalation and was due to free iodine. The radioactivity was excreted through both the urinary and intestinal tracts. Plasma IFNg levels did not significantly increase over time, and no significant HLA-DR induction on peripheral blood cells was detected. The highest radiation absorbed doses of 0.14 and 0.19 mGy/MBq were determined for the trachea and the lower intestines, respectively. The effective dose equivalent was 0.05 mSv/MBq.
  
  
  CONCLUSIONS
  After inhalation with the Pari-Master nebulizer, IFNg deposits normally in the lungs and shows no systemic effects in healthy volunteers.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Virgolini
authors.forename: A
authors.initials: A
authors.lastname: Kurtaran
authors.forename: M
authors.initials: M
authors.lastname: Leimer
authors.forename: P
authors.initials: P
authors.lastname: Smith-Jones
authors.forename: H
authors.initials: H
authors.lastname: Agis
authors.forename: P
authors.initials: P
authors.lastname: Angelberger
authors.forename: K
authors.initials: K
authors.lastname: Kletter
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.forename: W
authors.initials: W
authors.lastname: Linkesch
authors.forename: H G
authors.initials: HG
authors.lastname: Eichler
mesh_terms: D000280:Administration, Inhalation; D005260:Female; D006207:Half-Life; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011877:Radionuclide Imaging; D011994:Recombinant Proteins; D012016:Reference Values
chemical_list: D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D007371:Interferon-gamma