Evaluation ofLung Mucociliary Transport and Clearance in Ferrets: Imaging Nebulized Radioaerosols

Introduction: Mucociliary clearance dysfunction leads to a myriad of airway diseases, including ciliary dyskinesia, bronchiectasis, idiopathic pulmonary fibrosis and cystic fibrosis (CF). Thus, non-invasively imaging of inhaled radioaerosols with varying particle size, particle deposition with planar scintigraphy or positron emission tomography (PET) imaging, may offer a method of choice to understand pathophysiology of lung mucociliary transport, clearance and will facilitate the evaluation of CF therapies.

Objectives: The objective of the study is to visualize mucociliary transport and clearance using ^99mTc sulfur colloid or [¹⁸F] fluoride alumina nanoparticles in a CF ferret model that reflects the full spectrum of CF phenotypes observed in human patients.

Methods: [¹⁸F]fluoride alumina nanoparticles were synthesized as previously reported (J Nucl Med May 1, 2019 vol. 60 no. supplement 1 293). [^99mTc]Tc-sulfur colloid was obtained from our Nuclear Pharmacy. Wild type ferrets were used in this preliminary study. [¹⁸F]fluoride alumina nanoparticles (15 mCi in 3 mL of saline) were nebulized with Insta/Vent™ Plus Radioaerosol Lung Imaging System. [^99mTc]Tc-sulfur colloid (15 mCi in 3 mL of saline) were nebulized using Omron C801 nebulizer delivered with oxygen flowing at 4 L/min. A 5-minute nebulization was carried out for both the scans. PET scans were obtained in dynamic mode for 60 minutes, along with a CT scan for attenuation correction. Planar imaging was obtained in the prone position for 60 min.

Results: Despite modest radioaerosol delivery (<0.1% with clinically used nebulizers) we achieved radioaerosol deposition in the ferrets. [¹⁸F]fluoride alumina nanoparticles and [^99mTc]Tc-sulfur colloid were deposited in trachea and lungs within 5 minutes. At 60 minutes, 60% tracheal clearance is observed from the PET images, while 25% tracheal clearance is observed from the planar images. A homogeneous distribution and limited clearance from lungs are observed for both aerosols at later time points.

Conclusions: The [¹⁸F]fluoride alumina nanoparticles and [^99mTc]Tc-sulfur colloids were nebulized and delivered to the respiratory tract of ferrets. The [¹⁸F]fluoride alumina nanoparticles had good clearance from trachea. Most of the mucociliary transportation and clearance happened in the first few minutes of the study.

• Download figure
• Open in new tab
• Download powerpoint