Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study

Anushi E Rajapaksa; Lien Anh Ha Do; Darren Suryawijaya Ong; Magdy Sourial; Duncan Veysey; Richard Beare; William Hughes; William Yang; Robert J Bischof; Amarin McDonnell; Peter Eu; Leslie Y Yeo; Paul V Licciardi; Edward K Mulholland

doi:10.3389/fphar.2020.01291

Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study

Front Pharmacol. 2020 Aug 19:11:1291. doi: 10.3389/fphar.2020.01291. eCollection 2020.

Authors

Anushi E Rajapaksa^{1

2

3}, Lien Anh Ha Do^{1

4}, Darren Suryawijaya Ong^{1

4}, Magdy Sourial⁵, Duncan Veysey⁶, Richard Beare^{7

8}, William Hughes¹, William Yang¹, Robert J Bischof^{9

10}, Amarin McDonnell¹¹, Peter Eu¹², Leslie Y Yeo¹¹, Paul V Licciardi^{1

4}, Edward K Mulholland^{1

2

13}

Affiliations

¹ New Vaccines, Murdoch Children's Research Institute, Parkville, VIC, Australia.
² Neonatal Research, Royal Children's Hospital, Parkville, VIC, Australia.
³ Newborn Research, Royal Women's Hospital, Parkville, VIC, Australia.
⁴ Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
⁵ Animal Model Unit, The Royal Children's Hospital, Parkville, VIC, Australia.
⁶ Nuclear Imaging, The Royal Children's Hospital, Parkville, VIC, Australia.
⁷ Developmental Imaging, Murdoch Children's Research Institute, Parkville, VIC, Australia.
⁸ Department of Medicine, Monash University, Melbourne, VIC, Australia.
⁹ The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
¹⁰ School of Health and Life Sciences, Federation University, Berwick, VIC, Australia.
¹¹ School of Engineering, Royal Melbourne Institute of Technology, Melbourne, VIC, Australia.
¹² Department of Cancer Imaging, Peter MacCallum Cancer Centre, Parkville, VIC, Australia.
¹³ Department of Disease Control, London School of Tropical Medicine and Hygiene, London, United Kingdom.

Abstract

Objective: Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs.

Design: Prospective animal study.

Setting: Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children's Research Institute, Melbourne, Australia.

Subjects: Four weaned Border-Leicester/Suffolk lambs at 5 months of age.

Interventions: Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go^® or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure.

Measurements and main results: Both the HYDRA and AeroNeb Go^® produced palivizumab aerosols in the 1-5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 μm, range = 0.54-5.41μm) and the AeroNeb Go^® (3.07 ± 1.56 μm, range = 0.86-10 μm). Aerosolized palivizumab was delivered to the lungs at 88.79-94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung.

Conclusions: Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections.

Keywords: lamb model; monoclonal antibody; nebulization; palivizumab; prophylactic; respiratory syncytial virus.