title: Pharmacokinetic modeling of a novel hypoxia PET tracer [18F]HX4 in patients with non-small cell lung cancer.
abstract: BACKGROUND
  [18F]HX4 is a promising new PET tracer developed to identify hypoxic areas in tumor tissue. This study analyzes [18F]HX4 kinetics and assesses the performance of simplified methods for quantification of [18F]HX4 uptake. To this end, eight patients with non-small cell lung cancer received dynamic PET scans at three different time points (0, 120, and 240 min) after injection of 426 ± 72 MBq [18F]HX4, each lasting 30 min. Several compartment models were fitted to time activity curves (TAC) derived from various areas within tumor tissue using image-derived input functions.
  
  
  RESULTS
  Best fits were obtained using the reversible two-tissue compartment model with blood volume parameter (2T4k+VB). Simplified measures correlated well with VTestimates (tumor-to-blood ratio (TBr) R2= 0.96, tumor-to-muscle ratio R2= 0.94, standardized uptake value R2= 0.89).
  
  
  CONCLUSIONS
  [18F]HX4 shows reversible kinetics in tumor tissue: 2T4k+VB. TBr based on static imaging at 2 or 4 h can be used for quantification of [18F]HX4 uptake.
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.|Department of Nuclear Medicine & Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Verwer
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: C 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 Center, Maastricht, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: van Elmpt
authors.affiliation: Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Wierts
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: A D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|Department of Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: F M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Lambin
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. r.boellaard@vumc.nl.|Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands. r.boellaard@vumc.nl.
authors.forename: R
authors.initials: R
authors.lastname: Boellaard
keywords: 18F-3-Fluoro-2-(4-((2-Nitro-1H-Imidazol-1-yl)Methyl)-1H-1,2,3-Triazol-1-yl)Propan-1-ol ([18F]HX4); Hypoxia; Image-derived input function (IDIF); Molecular imaging; Non-small cell lung cancer (NSCLC); Positron emission tomography (PET); Standardized uptake value (SUV); Tracer kinetic modeling; Tumor-to-blood ratio