Clinical application of autologous technetium-99m-labelled eosinophils to detect focal eosinophilic inflammation in the lung.

This is the final version of the article. It first appeared from the BMJ Group via http://dx.doi.org/10.1136/thoraxjnl-2015-207156The detection of focal eosinophilic inflammation by non-invasive means may aid the diagnosis and follow-up of a variety of pulmonary pathologies. All current methods of detection involve invasive sampling, which may be contraindicated or too high-risk to be performed safely. The use of injected autologous technetium-99m (Tc-99m)-labelled eosinophils coupled to single-photon emission computed tomography (SPECT) has been demonstrated to localise eosinophilic inflammation in the lungs of a patient with antineutrophil cytoplasmic antibody-positive vasculitis. Here, we report on the utility of this technique to detect active eosinophilic inflammation in a patient with focal lung inflammation where a biopsy was contraindicated.The authors thank all the staff at the Department of Nuclear Medicine at Addenbrooke’s Hospital and the Wellcome Trust Clinical Research Facility, Cambridge; Cambridge Biomedical Research Centre Core Biochemistry Assay Laboratory; and the National Institute for Health Research, through the Comprehensive Clinical Research Network. This work was supported by Asthma-UK [08/11], the Medical Research Council [grant number MR/J00345X/1], the Wellcome Trust [grant number 098351/Z/12/Z], and Cambridge NIHR Biomedical Research Centre. Written informed consent was obtained in accordance with the Declaration of Helsinki. The study was approved by Cambridgeshire Research Ethics Committee (09/H0308/119) and the Administration of Radioactive Substances Advisory Committee of the United Kingdom (83/3130/25000)

Lesson of the month: novel method to quantify neutrophil uptake in early lung cancer using SPECT-CT

Neutrophils play an important role in the lung tumour microenvironment. We hypothesised that radiolabelled neutrophils coupled to single-photon emission CT (SPECT) may non-invasively quantify neutrophil uptake in tumours from patients with non-small cell lung cancer. We demonstrated increased uptake of radiolabelled neutrophils from the blood into tumours compared with non-specific uptake using radiolabelled transferrin. Moreover, indium-111-neutrophil activity in the tumour biopsies also correlated with myeloperoxidase (MPO)-positive neutrophils. Our data support the utility of imaging with In-111-labelled neutrophils and SPECT-CT to quantify neutrophil uptake in lung cancer

In vivo imaging reveals increased eosinophil uptake in the lungs of obese asthmatic patients.

To The Editor: Eosinophils play an important pathogenic role in pulmonary and systemic conditions including eosinophilic asthma and eosinophilic granulomatosis with polyangiitis.1,2 While progress has been made in understanding the mechanisms responsible for the activation of these cells, existing biomarkers of eosinophilic inflammation are indirect and/or invasive and do not always correlate with tissue eosinophilia. Hence, there is a need to develop non-invasive biomarkers of tissue eosinophilia. We have previously demonstrated the capacity of SPECT (single photon emission computed tomography) to quantify neutrophil uptake into the lungs of COPD patients.3 We sought to determine whether this methodology could be used to quantify eosinophil kinetics and pulmonary uptake, which may differ amongst diseases characterized by eosinophilic inflammation. In particular, the role of the eosinophil in asthma with obesity, a distinct asthma endotype associated with increased severity,4 is controversial. We hypothesized that injection of radiolabeled eosinophils, coupled with SPECT/CT, would reveal changes in eosinophil kinetics in patients compared to healthy volunteers.This work was supported by Asthma UK [08/11], the Medical Research Council [grant number MR/J00345X/1], the Wellcome Trust [grant number 098351/Z/12/Z], Cambridge NIHR Biomedical Research Centre, Wellcome Trust Senior Fellowship (to CEB) [grant number WT082265], AirPROM 7th EU Framework grant and Leicester NIHR Biomedical Research Centre

Lesson of the month: novel method to quantify neutrophil uptake in early lung cancer using SPECT-CT

Neutrophils play an important role in the lung tumour microenvironment. We hypothesised that radiolabelled neutrophils coupled to single-photon emission CT (SPECT) may non-invasively quantify neutrophil uptake in tumours from patients with non-small cell lung cancer. We demonstrated increased uptake of radiolabelled neutrophils from the blood into tumours compared with non-specific uptake using radiolabelled transferrin. Moreover, indium-111-neutrophil activity in the tumour biopsies also correlated with myeloperoxidase (MPO)-positive neutrophils. Our data support the utility of imaging with In-111-labelled neutrophils and SPECT-CT to quantify neutrophil uptake in lung cancer

Radiolabelled leucocytes in human pulmonary disease.

INTRODUCTION: Radionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of leucocyte kinetics, to the next goal of positron emission tomography (PET). SOURCES OF DATA: Mostly the authors' own studies, following on from studies of the early pioneers. AREAS OF CONTROVERSY: From early imaging studies, it appeared that the majority of the marginated granulocyte pool was located in the lungs. However, later work disputed this by demonstrating the exquisite sensitivity of granulocytes to ex vivo isolation and labelling, and that excessive lung activity is artefactual. AREAS OF AGREEMENT: Following refinement of labelling techniques, it was shown that the majority of marginated granulocytes are located in the spleen and bone marrow. The majority of leucocytes have a pulmonary vascular transit time only a few seconds longer than erythrocytes. The minority showing slow transit, ~5% in healthy persons, is increased in systemic inflammatory disorders that cause neutrophil priming and loss of deformability. Using a range of imaging techniques, including gamma camera imaging, whole-body counting and single photon-emission computerized tomography, labelled granulocytes were subsequently used to image pulmonary trafficking in lobar pneumonia, bronchiectasis, chronic obstructive pulmonary disease and adult respiratory distress syndrome. GROWING POINTS: More recently, eosinophils have been separated in pure form using magnetic bead technology for the study of eosinophil trafficking in asthma. AREAS TIMELY FOR DEVELOPING RESEARCH: These include advancement of eosinophil imaging, development of monocyte labelling, development of cell labelling with PET tracers and the tracking of lymphocytes.Asthma UK, NIHR Cambridge Biomedical Research Centre, Royal Papworth Hospital, AstraZeneca, GlaxoSmithKlin

Use of 111-Indium-labelled autologous eosinophils to establish the in vivo kinetics of human eosinophils in healthy subjects

Eosinophils are the major cellular effectors of allergic inflammation and represent an important therapeutic target. Whilst the genesis and activation of eosinophils has been extensively explored, little is known about their intravascular kinetics or physiological fate. This study was designed to determine the intravascular lifespan of eosinophils, their partitioning between circulating and marginated pools, and sites of disposal in healthy individuals. Using autologous, minimally manipulated 111-Indium-labelled leukocytes with blood sampling, we measured the eosinophil intravascular residence time as 25.2 hours (compared to 10.3 hours for neutrophils) and demonstrated a substantial marginated eosinophil pool. Gamma camera imaging studies using purified eosinophils demonstrated initial retention in the lungs, with early re-distribution to the liver and spleen, and evidence of re-circulation from a hepatic pool. This work provides the first in vivo measurements of eosinophil kinetics in healthy volunteers and shows that 111-Indium-labelled-eosinophils can be used to monitor the fate of eosinophils non-invasively

Response to Huisstede et al. Increased eosinophil uptake in the lungs of obese asthmatics – to correct for obesity compare to obese controls

To The Editor: We thank Huisstede and colleagues for their interest in our publication and their comments.1 Like the authors we agree wholeheartedly that weight reduction is key to improving asthma control and quality of life in obese patients, and that bariatric surgery is one treatment option to help achieve this. However, access to bariatric surgery varies between countries. In the UK, this option is only available for patients with a BMI range of 35-40 together with additional medical problems such as type 2 diabetes or high blood pressure proven to be improved by marked weight loss, or a BMI >40. This does not include the obese asthmatics that took part in our study (mean BMI of 28). We note that while Huisstede and colleagues found no difference in the eosinophil count between obese asthmatics and obese controls in their analysis,2 their patients were a very different cohort (with a BMI >45) compared to our group. Therefore we believe it is difficult to draw comparisons between the two studies.This work was supported by Asthma UK [08/11], the Medical Research Council [grant number MR/J00345X/1], the Wellcome Trust [grant number 098351/Z/12/Z], Cambridge NIHR Biomedical Research Centre, Wellcome Trust Senior Fellowship (to CEB) [grant number WT082265], AirPROM 7th EU Framework grant and Leicester NIHR Biomedical Research Centre