title: Response Monitoring with [18F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases.
abstract: The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases.
  
  
  
  Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [18F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression.
  
  
  
  5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [18F]FLT SUVmeanand SUVmaxwere significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUVmaxat days -1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [18F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADCmean) did not change in 5-FU-treated rats compared to untreated rats.
  
  
  
  This study suggests that 5-FU treatment induces a flare in [18F]FLT uptake of responsive CC531 tumors in the liver, while the ADCmeandid not change significantly. Future studies in larger groups are warranted to further investigate whether [18F]FLT PET can discriminate between disease progression and treatment response.
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. sandra.heskamp@radboudumc.nl.
authors: Sandra
authors: 0000-0001-7250-0846
authors: S
authors: Heskamp
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Linda
authors: L
authors: Heijmen
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Danny
authors: D
authors: Gerrits
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Janneke D M
authors: JDM
authors: Molkenboer-Kuenen
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Edwin G W
authors: EGW
authors: Ter Voert
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors: Kathrin
authors: K
authors: Heinzmann
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors: Davina J
authors: DJ
authors: Honess
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors: Donna-Michelle
authors: DM
authors: Smith
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors: John R
authors: JR
authors: Griffiths
authors: LBI, CRI - UMR 1149 Inserm, Université Paris Diderot, Paris, France.
authors: Sabrina
authors: S
authors: Doblas
authors: BHF Centre of Excellence, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, SE1 7EH, UK.
authors: Ralph
authors: R
authors: Sinkus
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Peter
authors: P
authors: Laverman
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Wim J G
authors: WJG
authors: Oyen
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Arend
authors: A
authors: Heerschap
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Otto C
authors: OC
authors: Boerman
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015224:Dideoxynucleosides / Q000494:pharmacology / Q000627:therapeutic use*; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D049268:Positron-Emission Tomography; D051381:Rats; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D015224:Dideoxynucleosides; C002854:alovudine; D005472:Fluorouracil
keywords: 5-Fluorouracil; Colorectal cancer; Diffusion-weighted MRI; Response monitoring; [18F]FLT PET