RESUMEN
PET with 18F-FDG has been increasingly applied, predominantly in the research setting, to study drug effects and pulmonary biology and to monitor disease progression and treatment outcomes in lung diseases that interfere with gas exchange through alterations of the pulmonary parenchyma, airways, or vasculature. To date, however, there are no widely accepted standard acquisition protocols or imaging data analysis methods for pulmonary 18F-FDG PET/CT in these diseases, resulting in disparate approaches. Hence, comparison of data across the literature is challenging. To help harmonize the acquisition and analysis and promote reproducibility, we collated details of acquisition protocols and analysis methods from 7 PET centers. From this information and our discussions, we reached the consensus recommendations given here on patient preparation, choice of dynamic versus static imaging, image reconstruction, and image analysis reporting.
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Consenso , Fluorodesoxiglucosa F18 , Enfermedades Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Guías de Práctica Clínica como Asunto , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Procesamiento de Imagen Asistido por Computador , Inyecciones , Enfermedades Pulmonares/fisiopatología , Posicionamiento del Paciente , RespiraciónRESUMEN
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.
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Neoplasias Pulmonares/diagnóstico por imagen , Neutrófilos , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Biopsia , Femenino , Humanos , Radioisótopos de Indio , Neoplasias Pulmonares/patología , Masculino , Estadificación de NeoplasiasRESUMEN
Treatment with the CXCR4 antagonist, plerixafor (AMD3100), has been proposed for clinical use in patients with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome and in pulmonary fibrosis. However, there is controversy with respect to the impact of plerixafor on neutrophil dynamics in the lung, which may affect its safety profile. In this study, we investigated the kinetics of endogenous neutrophils by direct imaging, using confocal intravital microscopy in mouse bone marrow, spleen, and lungs. Neutrophils are observed increasing their velocity and exiting the bone marrow following plerixafor administration, with a concomitant increase in neutrophil numbers in the blood and spleen, while the marginated pool of neutrophils in the lung microvasculature remained unchanged in terms of numbers and cell velocity. Use of autologous radiolabeled neutrophils and SPECT/CT imaging in healthy volunteers showed that plerixafor did not affect GM-CSF-primed neutrophil entrapment or release in the lungs. Taken together, these data suggest that plerixafor causes neutrophil mobilization from the bone marrow but does not impact on lung marginated neutrophil dynamics and thus is unlikely to compromise respiratory host defense both in humans and mice.
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Médula Ósea/efectos de los fármacos , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/farmacología , Pulmón/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Bazo/efectos de los fármacos , Animales , Bencilaminas , Médula Ósea/diagnóstico por imagen , Médula Ósea/inmunología , Rastreo Celular/métodos , Ciclamas , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/inmunología , Humanos , Recuento de Leucocitos , Pulmón/citología , Pulmón/diagnóstico por imagen , Pulmón/inmunología , Ratones Endogámicos C57BL , Neutrófilos/citología , Neutrófilos/inmunología , Radiofármacos/administración & dosificación , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Bazo/citología , Bazo/diagnóstico por imagen , Bazo/inmunología , Tecnecio/administración & dosificaciónRESUMEN
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.
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Pulmón/diagnóstico por imagen , Neutrófilos/fisiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Anciano , Biomarcadores/sangre , Femenino , Humanos , Interleucina-6/sangre , Lipopolisacáridos , Masculino , Persona de Mediana Edad , Infiltración Neutrófila/efectos de los fármacos , Infiltración Neutrófila/fisiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Reproducibilidad de los Resultados , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , TecnecioAsunto(s)
Asma/inmunología , Eosinófilos/inmunología , Pulmón/inmunología , Obesidad/inmunología , Anciano , Asma/diagnóstico por imagen , Eosinofilia/diagnóstico por imagen , Eosinofilia/inmunología , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico por imagen , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
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.
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Granulocitos/metabolismo , Marcaje Isotópico , Leucocitos , Enfermedades Pulmonares/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radioisótopos/metabolismo , Humanos , Leucocitos/fisiología , Enfermedades Pulmonares/patologíaRESUMEN
Blood is arguably the most important bodily fluid and its analysis provides crucial health status information. A first routine measure to narrow down diagnosis in clinical practice is the differential blood count, determining the frequency of all major blood cells. What is lacking to advance initial blood diagnostics is an unbiased and quick functional assessment of blood that can narrow down the diagnosis and generate specific hypotheses. To address this need, we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of diluted whole blood, without labeling, enrichment or separation, at rates of 1000 cells/sec. In a drop of blood we can identify all major blood cells and characterize their pathological changes in several disease conditions in vitro and in patient samples. This approach takes previous results of mechanical studies on specifically isolated blood cells to the level of application directly in blood and adds a functional dimension to conventional blood analysis.