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Use of autologous 99mTechnetium-labelled neutrophils to quantify lung neutrophil clearance in COPD

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Title: Use of autologous 99mTechnetium-labelled neutrophils to quantify lung neutrophil clearance in COPD
Authors: Tregay, N
Begg, M
Cahn, A
Farahi, N
Povey, K
Madhavan, S
Simmonds, R
Gillett, D
Solanki, C
Wong, A
Maison, J
Lennon, M
Bradley, G
Jarvis, E
De Groot, M
Wilson, F
Babar, J
Peters, AM
Hessel, EM
Chilvers, ER
Item Type: Journal Article
Abstract: RATIONALE: There is a need to develop imaging protocols which assess neutrophilic inflammation in the lung. AIM: To quantify whole lung neutrophil accumulation in (1) healthy volunteers (HV) following inhaled lipopolysaccharide (LPS) or saline and (2) patients with COPD using radiolabelled autologous neutrophils and single-photon emission computed tomography/CT (SPECT/CT). METHODS: 20 patients with COPD (Global initiative for chronic obstructive lung disease (GOLD) stages 2-3) and 18 HVs were studied. HVs received inhaled saline (n=6) or LPS (50 µg, n=12) prior to the injection of radiolabelled cells. Neutrophils were isolated using dextran sedimentation and Percoll plasma gradients and labelled with 99mTechnetium (Tc)-hexamethylpropyleneamine oxime. SPECT was performed over the thorax/upper abdomen at 45 min, 2 hours, 4 hours and 6 hours. Circulating biomarkers were measured prechallenge and post challenge. Blood neutrophil clearance in the lung was determined using Patlak-Rutland graphical analysis. RESULTS: There was increased accumulation of 99mTc-neutrophils in the lungs of patients with COPD and LPS-challenged subjects compared with saline-challenged subjects (saline: 0.0006±0.0003 mL/min/mL lung blood distribution volume [mean ±1 SD]; COPD: 0.0022±0.0010 mL/min/mL [p<0.001]; LPS: 0.0025±0.0008 mL/min/mL [p<0.001]). The accumulation of labelled neutrophils in 10 patients with COPD who underwent repeat radiolabelling/imaging 7-10 days later was highly reproducible (0.0022±0.0010 mL/min/mL vs 0.0023±0.0009 mL/min/mL). Baseline interleukin (IL)-6 levels in patients with COPD were elevated compared with HVs (1.5±1.06 pg/mL [mean ±1 SD] vs 0.4±0.24 pg/mL). LPS challenge increased the circulating IL-6 levels (7.5±2.72 pg/mL) 9 hours post challenge. CONCLUSIONS: This study shows the ability to quantify 'whole lung' neutrophil accumulation in HVs following LPS inhalation and in subjects with COPD using autologous radiolabelled neutrophils and SPECT/CT imaging. Moreover, the reproducibility observed supports the feasibility of using this approach to determine the efficacy of therapeutic agents aimed at altering neutrophil migration to the lungs.
Issue Date: 23-Jan-2019
Date of Acceptance: 10-Dec-2018
URI: http://hdl.handle.net/10044/1/67468
DOI: https://dx.doi.org/10.1136/thoraxjnl-2018-212509
ISSN: 1468-3296
Publisher: BMJ Publishing Group
Journal / Book Title: Thorax
Copyright Statement: © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/
Keywords: copd pathology
imaging/ct mri etc
innate immunity
neutrophil biology
1103 Clinical Sciences
Respiratory System
Publication Status: Published online
Conference Place: England
Online Publication Date: 2019-01-23
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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