title: Hypoxia imaging with [¹⁸F]HX4 PET in NSCLC patients: defining optimal imaging parameters.
abstract: OBJECTIVE
  [(18)F]HX4 is a promising hypoxia PET-tracer. Uptake, spatio-temporal stability and optimal acquisition parameters for [(18)F]HX4 PET imaging were evaluated in non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  [(18)F]HX4 PET/CT images of 15 NSCLC patients were acquired 2h and 4h after injection (p.i.). Maximum standardized-uptake-value (SUV(max)), tumor-to-blood-ratio (TBR(max)), hypoxic fraction (HF) and contrast-to-noise-ratio (CNR) were determined for all lesions. To evaluate spatio-temporal stability, DICE-similarity and Pearson correlation coefficients were calculated. Optimal acquisition-duration was assessed by comparing 30, 20, 10 and 5 min acquisitions.
  
  
  RESULTS
  Considerable uptake (TBR >1.4) was observed in 18/25 target lesions. TBR(max) increased significantly from 2 h (1.6 ± 0.3) to 4 h p.i. (2.0 ± 0.6). Uptake patterns at 2 h and 4 h p.i. showed a strong correlation (R=0.77 ± 0.10) with a DICE similarity coefficient of 0.69 ± 0.08 for the 30% highest uptake volume. Reducing acquisition-time resulted in significant changes in SUV(max) and CNR. TBR(max) and HF were only affected for scan-times of 5 min.
  
  
  CONCLUSIONS
  The majority of NSCLC lesions showed considerable [(18)F]HX4 uptake. The heterogeneous uptake pattern was stable between 2 h and 4 h p.i. [(18)F]HX4 PET imaging at 4 h p.i. is superior to 2 h p.i. to reach highest contrast. Acquisition time may be reduced to 10 min without significant effects on TBR(max) and HF.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. Electronic address: karen.zegers@maastro.nl.
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.forename: Wouter
authors.initials: W
authors.lastname: van Elmpt
authors.forename: Roel
authors.initials: R
authors.lastname: Wierts
authors.forename: Bart
authors.initials: B
authors.lastname: Reymen
authors.forename: Hoda
authors.initials: H
authors.lastname: Sharifi
authors.forename: Michel C
authors.initials: MC
authors.lastname: Öllers
authors.forename: Frank
authors.initials: F
authors.lastname: Hoebers
authors.forename: Esther G C
authors.initials: EG
authors.lastname: Troost
authors.forename: Rinus
authors.initials: R
authors.lastname: Wanders
authors.forename: Angela
authors.initials: A
authors.lastname: van Baardwijk
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Brans
authors.forename: Jonas
authors.initials: J
authors.lastname: Eriksson
authors.forename: Bert
authors.initials: B
authors.lastname: Windhorst
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000473:pathology; D015687:Cell Hypoxia; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007093:Imidazoles; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D014230:Triazoles
chemical_list: D005462:Fluorine Radioisotopes; C562168:HX4 compound; D007093:Imidazoles; D019275:Radiopharmaceuticals; D014230:Triazoles
keywords: HX4; Hypoxia; Imaging; NSCLC; PET