- Title
- Pulmonary deposition of radionucleotide-labeled palivizumab : proof-of-concept study
- Creator
- Rajapaksa, Anushi; Do, Lien; Suryawijaya Ong, Darren; Sourial, Magdy; Bischof, Robert
- Date
- 2020
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/174401
- Identifier
- vital:14859
- Identifier
-
https://doi.org/10.3389/fphar.2020.01291
- Identifier
- ISBN:1663-9812 (ISSN)
- 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. © Copyright © 2020 Rajapaksa, Do, Suryawijaya Ong, Sourial, Veysey, Beare, Hughes, Yang, Bischof, McDonnell, Eu, Yeo, Licciardi and Mulholland. ***Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Robert Bishof” is provided in this record***; The authors thank Rebecca Sutton for her technical assistance on lamb management, and Kera Pethybridge and Ellie Wright for her technical assistance on nuclear imaging. This study is?supported by a Jack Brockhoff Foundation Early Career Research Grant and a National Health and Medical Research Council (NHMRC) Early Career Fellowship (GNT1123030) awarded to AR, and the Victorian Government?s Operational Infrastructure Support Program. PL is supported by an NHMRC Career Development Fellowship (GNT1165084).
- Publisher
- Frontiers Media S.A.
- Relation
- Frontiers in Pharmacology Vol. 11, no. (2020), p.
- Rights
- Metadata is freely available under a CCO license
- Rights
- https://creativecommons.org/licenses/by/4.0/
- Rights
- Copyright © 2020 Rajapaksa, Do, Suryawijaya Ong, Sourial, Veysey, Beare, Hughes, Yang, Bischof, McDonnell, Eu, Yeo, Licciardi and Mulholland. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
- Rights
- Open Access
- Subject
- 1115 Pharmacology and Pharmaceutical Sciences; Lamb model; Monoclonal antibody; Nebulization; Palivizumab; Prophylactic; Respiratory syncytial virus
- Full Text
- Reviewed
- Funder
- The authors thank Rebecca Sutton for her technical assistance on lamb management, and Kera Pethybridge and Ellie Wright for her technical assistance on nuclear imaging. This study is?supported by a Jack Brockhoff Foundation Early Career Research Grant and a National Health and Medical Research Council (NHMRC) Early Career Fellowship (GNT1123030) awarded to AR, and the Victorian Government?s Operational Infrastructure Support Program. PL is supported by an NHMRC Career Development Fellowship (GNT1165084).
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