PET/CT imaging-based quantification of respiratory tract deposition of small- and large-particle aerosols versus intranasal bolus in rodents

Abstract Objectives The size of airborne particles may influence where they deposit in the respiratory tract, the infectious dose, and disease progression. Intranasal bolus administration is often used as a substitute for aerosol exposure. Inhalational and intranasal exposure routes are commonly used in hamster and guinea pig models of infectious diseases. The aim of the present study was to compare regional respiratory tract deposition of small- and large-particle aerosols to intranasal bolus administration. Methods Golden hamsters were exposed to 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG)-radiolabeled aerosols with mass median aerodynamic diameters (MMADs) of 1.3 and 6.1 µm, and Hartley guinea pigs were exposed to 1.4 and 10.4 µm aerosols. Separately, hamsters and guinea pigs received bolus solutions of 18F-FDG (50 µL per naris) intranasally. Positron emission tomography–computed tomography (PET/CT) imaging was used to quantify the deposition of 18F-FDG in the respiratory tracts, including the oronasal cavities, tracheas/esophagi, and lungs. Results Smaller particle aerosols deposited in the lungs more efficiently than larger particle aerosols or intranasal bolus administration. Large-particle aerosol and intranasal bolus administration resulted in greater oronasal deposition than small-particle aerosol. Conclusions PET/CT imaging-based quantification enabled novel characterization of particle deposition in rodents and supports an inverse relationship between aerodynamic particle size and pulmonary deposition. The regional distribution of intranasal bolus administered FDG more closely resembled large-particle aerosols than small-particle aerosols. These findings may aid in understanding the infectivity and pathogenicity of bioaerosols based on particle size and raise concern about substituting intranasal administration for aerosol exposure. PLAIN LANGUAGE SUMMARY Many respiratory pathogens are transmitted via inhalation of contaminated microscopic particles. The size of these particles influences where they deposit in the respiratory tract, and subsequently whether and how disease develops. Although deposition of inhaled particles is well-described in humans, respiratory anatomy and physiology is significantly different in small-animal models routinely used in human infectious disease research. Our study included hamsters and guinea pigs to investigate the deposition difference within the respiratory tract between aerosolized small and large particles; for comparison, intranasal administration was also performed. We determined that aerosol particle size is crucial to determine where it settles. The smaller particles were more efficient at reaching the lungs than larger particles. Intranasal administration was less efficient than aerosol delivery suggesting the intranasal route is not a suitable substitute for aerosol exposure. This information may help further investigate infectious disease transmission and guide preventive and therapeutic strategies based on particle size.