Effect of Particle Size on the Regional Deposition of Inhaled Technitium-99m Labeled Particles in Rodents.

Abstract

There is extensive information detailing the deposition patterns of various particles in the human respiratory tracts and several manuscripts detailing deposition in preclinical species. However, the majority of the data in rodents was generated prior to significant advancements in rodent imaging capabilities. In order to address this need and determine the effect particle size has on the deposition patterns in rodent species these experiments were conducted. Rats and mice were exposed, via nose only inhalation, to particles ranging from 0.5 to 5 microns mass median aerodynamic diameter (MMAD). The aerosols were composed of technetium−99m radiolabeled sulfur colloid particles. Aerosols were generated with a series of compressed air jet nebulizers to achieve each desired particle size (0.5, 1.0, 3.0 and 5.0 micron). Aerosol samples were collected to characterize the activity aerosol concentration and the particle size distribution. Impactor analysis detailed that mass and activity median aerodynamic diameters (AMAD) correlated with each other. For example for the target particle size of 0.5 micron the MMAD was 0.62 micron and the AMAD was 0.57 micron. These data indicate that the aerosols of Tech−99m and the sulfur colloid particles were homogeneous. This trend of MMAD and AMAD agreement was consistent from 0.5 to 5 microns. In order to determine deposition animals were sacrificed immediately following inhalation exposures and were imaged using a small−animal SPECT−CT camera. Data analysis indicated that 11 Ci of material in lungs of the mouse and 60 Ci in the lungs of the rat after exposure to the 0.5 micron aerosol. Increasing particle size resulted in an increase in deposition in the nasal region and resulted in an increase in stomach uptake.