18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.

INTRODUCTION: Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18F-fluoro-2-deoxyglucose (18F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14C-2DG uptake in activated neutrophils. METHODS: Lung uptake of 18F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. RESULTS: Significant uptake of 18F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. CONCLUSION: Systemic endotoxin-induced ALI results in very early and progressive uptake of 18F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 18F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14C-2DG uptake in activated neutrophils. 18F-FDG PET may provide a potential mechanism for early diagnosis and therapeutic assessment of ALI/ARDS.

Comparison of whole-body PET/CT, dedicated high-resolution head and neck PET/CT, and contrast-enhanced CT in preoperative staging of clinically M0 squamous cell carcinoma of the head and neck.

UNLABELLED: The purpose of this study was to compare optimized whole-body (WB) and dedicated high-resolution contrast-enhanced PET/CT protocols and contrast enhanced CT in the preoperative staging of primary squamous cell carcinoma of the head and neck. METHODS: A total of 44 patients with clinically M0 squamous cell carcinoma of the head and neck underwent primary tumor resection and neck dissection within 6 wk of diagnostic imaging. Imaging consisted of a standard WB PET/CT protocol without intravenous contrast enhancement, followed by a high-resolution dedicated head and neck (HN) PET/CT protocol, which included diagnostic-quality contrast-enhanced CT (CECT). Imaging results were compared with histopathology. A 5-point scale was used to designate primary tumor localization and the presence of lymph node metastasis on a per-patient and per-level basis. For cervical nodes, receiver-operating-characteristic curves were generated to determine the differences in performance between the WB and HN PET/CT protocols and CECT. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for primary tumor and cervical nodes. RESULTS: No statistical difference was observed between WB and HN PET/CT protocols, both of which significantly outperformed CECT, in the evaluation of the primary tumor. The performance of the HN PET/CT protocol was superior to that of the WB PET/CT in the detection of cervical node metastases, achieving statistical significance on a per-level basis and approaching significance on a per-patient basis, with the greatest advantage in the detection of small positive lymph nodes (<15 mm). No significant difference was observed between the WB PET/CT protocol and CECT in nodal staging, either on a per-patient or on a per-level basis. CONCLUSION: The primary advantage of the dedicated HN PET/CT protocol over the WB protocol or CECT in the staging of head and neck cancer is in the detection of small lymph node metastases.