Reply to LTE, "Role of 18F-FDG PET/CT in Cardiac Sarcoid Detection and Therapy Monitoring: Addition to the Expert Consensus".

Abstract

293 Introduction: Mucociliary Clearance (MCC) is an innate respiratory host defense mechanism that removes inhaled and aspirated particles and pathogens from the airways. Defects in MCC contribute to many airway diseases such as primary ciliary dyskinesia, asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and cystic fibrosis. MCC has been visualized using inhaled aerosols containing insoluble Tc-99m labeled colloids with either planar scintigraphy or SPECT. However, the low temporal and spatial resolution of single photon imaging in this application makes it difficult to investigate the mechanisms of MCC defects in airways disease or to determine the efficacy of therapeutics. An imaging modality with higher temporal and spatial resolution, such as PET, will allow for quantitative measurement of MCC and opportunities to evaluate the efficacy of newer therapeutics. Objectives: The objective of the study was to develop a method to visualize and quantify MCC in pulmonary pathophysiology using PET imaging. Pre-clinical imaging was performed using a porcine model. Methods: [18F]-fluoride labeled alumina nanoparticles were obtained by adding aqueous [18F]-fluoride to γ-alumina nanoparticles (<50 nm). The suspension was incubated at room temperature with continuous shaking (20 min) followed by centrifugation (10 min). The unbound [18F]-fluoride was separated from the pellet, and the pellet was then washed with water, re-suspended, shaken (5 min) and centrifuged (5 min). The washing step was repeated two times, and the [18F]-fluoride alumina nanoparticles were formulated in saline. We used newborn piglets for this study. In one experiment, we targeted small distal airways by generating aerosols of [18F]-fluoride alumina nanoparticles in saline with mass median aerodynamic diameter (MMAD) of ~0.31 µm. We used 14 mCi with effective delivery of ~ 1 mCi into the airways. In another experiment, we targeted large proximal airways by generating aerosols of [18F]-fluoride alumina nanoparticles in saline with MMAD of ~10 µm. We delivered 1 mCi directly into the airways. An endotracheal tube was needed for the delivery of the aerosolized [18F]-fluoride alumina nanoparticles. Immediately after delivery of the aerosolized nanoparticles, the endotracheal tube was removed. The piglet breathed spontaneously throughout the study and maintained its own airway humidification. We obtained PET scans in list mode for a period of 60 minutes, along with a CT scan for attenuation correction. Decay- and attenuation-corrected data was binned into 30-second frames and the binned static images were used to assess MCC over time. Results: [18F]-fluoride alumina nanoparticles were obtained with radiochemical yields 95 ± 3% in < 70 minutes. Repeated washing of [18F]-labeled alumina nanoparticles with water and incubation in saline failed to release any significant [18F]-fluoride over 2-hour period. We achieved a diffuse and homogeneous delivery of the radiotracer regardless of whether a nebulizer or microsprayer was used. As predicted, the fine particles generated with the nebulizer deposited in distal airways. In contrast, the larger particles generated with a microsprayer deposited in proximal airways. With time, the radiotracer cleared out of the airways. Most of the clearance happened in the first few minutes of the study. Conclusions: A simple and highly efficient synthesis of [18F]-labeled alumina nanoparticles was developed and the [18F]-labeled alumina nanoparticles show good in vitro stability. The [18F]-labeled alumina nanoparticles were successfully delivered to pig airways via nebulizer or micro-sprayer. Varying the size of the droplets affected the deposition of the radioactivity within the airways. MCC clearance was observed using PET, with most of the clearance occurring within the first few minutes of radiotracer administration.