title: In vivo quantification of hypoxic and metabolic status of NSCLC tumors using [18F]HX4 and [18F]FDG-PET/CT imaging.
abstract: OBJECTIVE
  Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non-small cell lung cancer (NSCLC). PET imaging is a noninvasive technique that is frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using 2[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET and hypoxia using HX4-PET imaging.
  
  
  METHODS
  FDG- and HX4-PET/CT images of 25 patients with NSCLC were coregistered. At a global tumor level, HX4 and FDG parameters were extracted from the gross tumor volume (GTV). The HX4 high-fraction (HX4-HF) and HX4 high-volume (HX4-HV) were defined using a tumor-to-blood ratio > 1.4. For FDG high-fraction (FDG-HF) and FDG high-volume (FDG-HV), a standardized uptake value (SUV) > 50% of SUVmax was used. We evaluated the spatial correlation between HX4 and FDG uptake within the tumor, to quantify the (mis)match between volumes with a high FDG and high HX4 uptake.
  
  
  RESULTS
  At a tumor level, significant correlations were observed between FDG and HX4 parameters. For the primary GTV, the HX4-HF was three times smaller compared with the FDG-HF. In 53% of the primary lesions, less than 1 cm(3) of the HX4-HV was outside the FDG-HV; for 37%, this volume was 1.9 to 12 cm(3). Remarkably, a distinct uptake pattern was observed in 11%, with large hypoxic volumes localized outside the FDG-HV.
  
  
  CONCLUSIONS
  Hypoxic tumor volumes are smaller than metabolic active volumes. Approximately half of the lesions showed a good spatial correlation between the PET tracers. In the other cases, a (partial) mismatch was observed. The addition of HX4-PET imaging has the potential to individualize patient treatment.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands. karen.zegers@maastro.nl.
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: van Elmpt
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Reymen
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Aniek J G
authors.initials: AJ
authors.lastname: Even
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Esther G C
authors.initials: EG
authors.lastname: Troost
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Ollers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Frank J P
authors.initials: FJ
authors.lastname: Hoebers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Ruud M A
authors.initials: RM
authors.lastname: Houben
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Jonas
authors.initials: J
authors.lastname: Eriksson
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: Department of Nuclear Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands. Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands. University Hospitals Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007090:Image Interpretation, Computer-Assisted; D007091:Image Processing, Computer-Assisted; D007093:Imidazoles; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed; D014230:Triazoles
chemical_list: C562168:HX4 compound; D007093:Imidazoles; D019275:Radiopharmaceuticals; D014230:Triazoles; D019788:Fluorodeoxyglucose F18