title: Pharmacodynamic evaluation of irinotecan therapy by FDG and FLT PET/CT imaging in a colorectal cancer xenograft model.
abstract: OBJECTIVE
  Longitudinal changes of 3'-[(18) F]fluoro-3'-deoxythymidine (FLT) and 2-deoxy-2-[(18) F]fluoro-D-glucose (FDG) in response to irinotecan therapy in an animal model of colorectal cancer were compared.
  
  
  METHODS
  SCID/CB-17 mice with HCT116 tumors were treated with 50 mg/kg irinotecan by intraperitoneal injection weekly for 3 weeks. FLT and FDG-positron emission tomography (PET) were performed at baseline, the day after each treatment, and 5 days after the first treatment. Proliferation and apoptosis were evaluated by immunohistochemistry (IHC) after day 15 of imaging.
  
  
  RESULTS
  Irinotecan treatment resulted in a suppression of tumor growth. Tumor FLT uptake was decreased the day after each treatment but to a lesser extent 5 days after the first treatment. FDG uptake increased the day after each treatment with a continuous increase throughout the experiment. IHC analysis of phospho-H3 and Ki67 confirmed FLT-PET results, indicating a decrease in proliferation the day after the final irinotecan treatment. Increased apoptosis monitored by caspase-3 was observed after day 15 with irinotecan treatment.
  
  
  CONCLUSIONS
  FLT-PET may be a better method than FDG-PET for assessing treatment response to irinotecan. Changes in imaging occur before changes in tumor volume.
authors.affiliation: Translational Imaging and Biochemical Biomarkers, Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA. sarah.mudd@abbott.com
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Mudd
authors.forename: Kimberley D
authors.initials: KD
authors.lastname: Holich
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Voorbach
authors.forename: Todd B
authors.initials: TB
authors.lastname: Cole
authors.forename: David R
authors.initials: DR
authors.lastname: Reuter
authors.forename: Paul
authors.initials: P
authors.lastname: Tapang
authors.forename: Gail
authors.initials: G
authors.lastname: Bukofzer
authors.forename: Arunava
authors.initials: A
authors.lastname: Chakravartty
authors.forename: Cherrie K
authors.initials: CK
authors.lastname: Donawho
authors.forename: Joann P
authors.initials: JP
authors.lastname: Palma
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Fox
authors.forename: Mark
authors.initials: M
authors.lastname: Day
authors.forename: Yanping
authors.initials: Y
authors.lastname: Luo
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D051379:Mice; D016513:Mice, SCID; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D015224:Dideoxynucleosides; D019788:Fluorodeoxyglucose F18; D000077146:Irinotecan; C002854:alovudine; D002166:Camptothecin