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.

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

“…In this way budesonide and fluticasone propionate plasma levels can give a good indication on tissue levels [112]. Also, for salbutamol sulfate deposition by gamma scintigraphy and plasma levels showed very similar values (26.2% vs. 26.4%) [113]. Further, it has also been shown that deposition of budesonide is linked to local action.…”

Visualization and Estimation of Nasal Spray Delivery to Olfactory Mucosa in an Image-Based Transparent Nasal Model

“…The scattering of photons can cause distortions in scintigraphy images and lead to inaccurate dose quantification, with around 30% of photons being scattered and causing measurement errors. Other factors that can affect accuracy include the dosage administered before the study, aerosol radiolabeling quality control, and radioactivity recovery [ 27 ]. Furthermore, scintigraphy images are only 2D and cannot distinguish between multiple layers of deposition.…”