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

• Published in: Thorax Vol. 74; no. 7; pp. 659 - 666
• Main Authors: Tregay, Nicola, Begg, Malcolm, Cahn, Anthony, Farahi, Neda, Povey, Kathryn, Madhavan, Sujith, Simmonds, Rosalind, Gillett, Daniel, Solanki, Chandra, Wong, Anna, Maison, Joanna, Lennon, Mark, Bradley, Glyn, Jarvis, Emily, de Groot, Marius, Wilson, Fred, Babar, Judith, Peters, A Michael, Hessel, Edith M, Chilvers, Edwin R
• Format: Journal Article
• Language: English
• Published: England 01.07.2019
• Subjects: Aged; Biomarkers - blood; Female; Humans; Interleukin-6 - blood; Lipopolysaccharides; Lung - diagnostic imaging; Male; Middle Aged; Neutrophil Infiltration - drug effects; Neutrophil Infiltration - physiology; Neutrophils - physiology; Pulmonary Disease, Chronic Obstructive - diagnostic imaging; Pulmonary Disease, Chronic Obstructive - pathology; Reproducibility of Results; Single Photon Emission Computed Tomography Computed Tomography - methods; Technetium; copd pathology; neutrophil biology; innate immunity; imaging/ct mri etc
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thoraxjnl-2018-212509

There is a need to develop imaging protocols which assess neutrophilic inflammation in the lung. 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). 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 Technetium (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. There was increased accumulation of Tc-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. 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.