INHALATION SCINTIGRAPHY WITH IODINE-123-LABELED INTERFERON GAMMA-1B -PULMONARY DEPOSITION AND DOSE-ESCALATION STUDY IN HEALTHY-VOLUNTEERS

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 investig ate the dose response of escalating doses of inhaled I-123-labeled IFN g (I-123-IFNg) and its safety, biodistribution and radiation absorbed doses in healthy volunteers. Methods: IFNg was labeled with I-123 to p roduce a specific activity of 1800 MBq/mg of IFNg. The biological acti vities of I-123-IFNg, nebulized I-123-IFNg and unlabeled IFNg were eva luated in various functional in vitro tests. Ten healthy volunteers we re enrolled in the in vivo dose escalation study (180 MBq of I-123-IFN g diluted with 0.1-2 mg of INFg). Inhalation scintigraphy, using a Par i-Master nebulizer, was performed for up to 37 min, during which dynam ic posterior images of the lungs were obtained. Whole-body scanning wa s performed at various time points up to 24 hr postinjection, for biod istribution and dosimetry purposes. Blood, urine and feces were also c ollected over this 24-hr period. Lung perfusion scintigraphy with Tc-9 9m-microspheres was performed at the end of the study for attenuation correction. Results: Inhaled nebulized IFNg showed a uniform depositio n pattern in the lungs with deposition ratios of 0.74 (central-to-peri pheral) and 0.78 (upper-to-lower). The lung deposition of IFNg was tim e-dependent, with a deposition half-time between 1 and 5 min. Despite a large interindividual variation, the total lung deposition was propo rtional 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 o f IFNg), The biological half-life in the lung could be fitted to a bie xponential function, with resultant half-lives of 1 and 11 hr. Blood a ctivity was maximal at 3.5 hr after inhalation and was due to free iod ine. The radioactivity was excreted through both the urinary and intes tinal tracts. Plasma IFNg levels did not significantly increase over t ime, and no significant HLA-DR induction on peripheral blood cells was detected. The highest radiation absorbed doses of 0.14 and 0.19 mGy/M Bq were determined for the trachea and the lower intestines, respectiv ely. The effective dose equivalent was 0.05 mSv/MBq. Conclusion: After inhalation with the Pari-Master nebulizer, IFNg deposits normally in the lungs and shows no systemic effects in healthy volunteers.