Anatomic localization of 24- and 96-h particle retention in canine airways

Abstract

Long-term retention of particles in airways is controversial. However, precise anatomic localization of the particles is not possible in people. In this study the anatomic location of retained particles after shallow bolus inhalation was determined in anesthetized, ventilated beagle dogs. Fifty 30-cm(3) boluses containing monodisperse 2.5-micron polystyrene particles (PSL) were delivered to a shallow lung depth of 81-129 cm(3). At 96 h before euthanasia, red fluorescent PSL were used; at 24 h, green fluorescent PSL and (99m)Tc-labeled PSL were used. Clearance of (99m)Tc-PSL was measured during the next 24 h. Sites of particle retention were determined in systematic, volume-weighted random samples of microwave-fixed lung tissue. Precise particle localization and distribution was analyzed by using gamma counting, conventional fluorescence microscopy, and confocal microscopy. Within 24 h after shallow bolus inhalation, 50-95% of the deposited (99m)Tc-PSL were cleared, but the remaining fraction was cleared slowly in all dogs, similar to previous human results. The three-dimensional deposition patterns showed particles across the entire cross-sectional plane of the lungs at the level of the carina. In these locations, 33 +/- 9.9% of the retained particles were found in small, nonrespiratory airways (0.3- to 1-mm diameter) and 49 +/- 10% of the particles in alveoli; the remaining fraction was found in larger airways. After 96 h, a similar pattern was found. These findings suggest that long-term retention in airways is at the bronchiolar level.

Comparison of Clearance of Particles Inhaled With Bolus and Extremely Slow Inhalation Techniques

“…The rst interpretation is in agreement with earlier results with the extremely slow inhalation technique [ 15] and predictions with the USBG model for particle deposition in the lung. This interpretation is also in agreement with a study using shallow bolus inhalations in dogs by Kreyling et al [ 35] , who found considerable fractions of particles deposited in both the bronchiolar and the alveolar regions. In this experiment, volumetric lung depth varied between 40 and 100 ml, which represented 45% to 85% of the volume of the airways with no alveoli ( phase I ).…”

In vivo animal models for drug delivery across the lung mucosal barrier☆

“…Gamma scintigraphy is the most commonly used imaging method but single photon emission computed tomography (SPECT) and positron emission tomography (PET) are growing in popularity [149,150]. In general terms two major approaches have been adopted for imaging small animals: the first is the adaptation of clinical imaging technologies such as gamma scintigraphy, SPECT (Figure 4) [151] and PET to the smaller animal dimensions and the second is based on new evolving technologies based on whole-body photonic imaging [152].…”

“…A number of studies have used nuclear imaging to image radiolabelled drugs and particles delivered to small [153] and more commonly large [154,151,155158] animals.…”

Dosimetry of Inhaled Nanoparticles

“…This apparent difference between rodents and man in the retention time of particles in airways and hence their clearance from this lung compartment has to be utterly considered when extrapolating rodent data to man. The prolonged retention of MP was also observed in the airways of dogs (Kreyling et al 1999). As mentioned already in the previous paragraph, the mechanisms for prolonged retention and, hence, delayed clearance of particles from airways as observed in humans and dogs remain unclear.…”