title: Planar gamma scintigraphy--points to consider when quantifying pulmonary dry powder aerosol deposition.
abstract: Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (with 95% confidence interval of 24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.
authors.affiliation: AstraZeneca R&D Lund, SE-221 87, Lund, Sweden. eva.bondesson@astrazeneca.com
authors.forename: Eva
authors.initials: E
authors.lastname: Bondesson
authors.forename: Thomas
authors.initials: T
authors.lastname: Bengtsson
authors.forename: Lars
authors.initials: L
authors.lastname: Borgström
authors.forename: Lars Erik
authors.initials: LE
authors.lastname: Nilsson
authors.forename: Kristina
authors.initials: K
authors.lastname: Norrgren
authors.forename: Eva
authors.initials: E
authors.lastname: Trofast
authors.forename: Per
authors.initials: P
authors.lastname: Wollmer
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D002606:Charcoal / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011208:Powders; D011877:Radionuclide Imaging; D013667:Technetium
chemical_list: D000336:Aerosols; D011208:Powders; D002606:Charcoal; D013667:Technetium; D000420:Albuterol