title: Baseline [(18)F]FMISO μPET as a Predictive Biomarker for Response to HIF-1α Inhibition Combined with 5-FU Chemotherapy in a Human Colorectal Cancer Xenograft Model.
abstract: The purpose of this study was to characterize imaging biomarkers for the potential benefit of hypoxia-inducible factor-1 (HIF-1)α inhibition (by PX-12) during 5-fluorouracil (5-FU) chemotherapy in the treatment of colorectal cancer (CRC).
  
  
  
  Therapy response to 5-FU ± PX-12 was assessed with baseline [(18)F]fluoromisonidazole ([(18)F]FMISO) and longitudinal 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission computed tomography (μPET/CT) in CRC xenograft model (n = 36) during breathing of a hypoxic (10 % O2) or normoxic (21 % O2) atmosphere. Ex vivo, immunohistochemistry was performed.
  
  
  
  Baseline [(18)F]FMISO uptake and relative tumor volume (RTV) 2 days after 5-FU or 5-FU + PX-12 administration correlated significantly (p ≤ 0.01). Under hypoxic breathing conditions, [(18)F]FDG uptake (-53.1 ± 8.4 %) and Ki67 expression (-16 %) decreased and RTV stagnated in the 5-FU + PX-12 treatment group, but not in 5-FU alone-treated tumors. Under normoxic breathing, [(18)F]FDG uptake (-23.5 ± 15.2 % and -72.8 ± 7.1 %) and Ki67 expression (-5 % and -19 %) decreased and RTV stagnated in both the 5-FU and the combination treatment group, respectively.
  
  
  
  Baseline [(18)F]FMISO μPET may predict the beneficial effect of HIF-1α inhibition during 5-FU chemotherapy in CRC.
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: De Bruycker
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium.|Department of Nuclear Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium.
authors.forename: Christel
authors.initials: C
authors.lastname: Vangestel
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium.|Department of Nuclear Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Van den Wyngaert
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium.|Department of Nuclear Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium.
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Wouters
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, Belgium. sigrid.stroobants@uza.be.|Department of Nuclear Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium. sigrid.stroobants@uza.be.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D005260:Female; D005462:Fluorine Radioisotopes; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007150:Immunohistochemistry; D008819:Mice, Nude; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C031843:fluoromisonidazole; D008920:Misonidazole; D005472:Fluorouracil
keywords: 2-deoxy-2-[18F]fluoro-D-glucose; 5-fluorouracil; PX-12; Tumor hypoxia; [18F]fluoromisonidazole