title: [18F]EF3 is not superior to [18F]FMISO for PET-based hypoxia evaluation as measured in a rat rhabdomyosarcoma tumour model.
abstract: OBJECTIVE
  The aim of this investigation was to quantitatively compare the novel positron emission tomography (PET) hypoxia marker 2-(2-nitroimidazol-1-yl)-N-(3[(18)F],3,3-trifluoropropyl)acetamide ([(18)F]EF3) with the reference hypoxia tracer [(18)F]fluoromisonidazole ([(18)F]FMISO).
  
  
  METHODS
  [(18)F]EF3 or [(18)F]FMISO was injected every 2 days into two separate groups of rats bearing syngeneic rhabdomyosarcoma tumours. In vivo PET analysis was done by drawing regions of interest on the images of selected tissues. The resulting activity data were quantified by the percentage of injected radioactivity per gram tissue (%ID/g) and tumour to blood (T/B) ratio. The spatial distribution of radioactivity was defined by autoradiography on frozen tumour sections.
  
  
  RESULTS
  The blood clearance of [(18)F]EF3 was faster than that of [(18)F]FMISO. The clearance of both tracers was slower in tumour tissue compared with other tissues. This results in increasing T/B ratios as a function of time post tracer injection (p.i.). The maximal [(18)F]EF3 tumour uptake, compared to the maximum [(18)F]FMISO uptake, was significantly lower at 2 h p.i. but reached similar levels at 4 h p.i. The tumour uptake for both tracers was independent of the tumour volume for all investigated time points. Both tracers showed heterogeneous intra-tumoural distribution.
  
  
  CONCLUSIONS
  [(18)F]EF3 tumour uptake reached similar levels at 4 h p.i. compared with tumour retention observed after injection of [(18)F]FMISO at 2 h p.i. Although [(18)F]EF3 is a promising non-invasive tracer, it is not superior over [(18)F]FMISO for the visualisation of tumour hypoxia. No significant differences between [(18)F]EF3 and [(18)F]FMISO were observed with regard to the intra-tumoural distribution and the extra-tumoural tissue retention.
authors.affiliation: Department of Nuclear Medicine, University Hospital Gasthuisberg and KU Leuven, 3000, Leuven, Belgium. ludwig.dubois@maastro.unimaas.nl
authors.forename: Ludwig
authors.initials: L
authors.lastname: Dubois
authors.forename: Willy
authors.initials: W
authors.lastname: Landuyt
authors.forename: Lieselotte
authors.initials: L
authors.lastname: Cloetens
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.forename: Johan
authors.initials: J
authors.lastname: Nuyts
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.forename: Luc
authors.initials: L
authors.lastname: Mortelmans
mesh_terms: D000818:Animals; D001345:Autoradiography; D015415:Biomarkers / Q000378:metabolism; D006321:Heart / Q000502:physiology; D000860:Hypoxia / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008920:Misonidazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009206:Myocardium / Q000166:cytology; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D051381:Rats; D012016:Reference Values; D012208:Rhabdomyosarcoma / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: C438056:2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)-acetamide; D015415:Biomarkers; D009593:Nitroimidazoles; C031843:fluoromisonidazole; D008920:Misonidazole