title: Evaluation of 2-deoxy-2-[18F]fluoro-D-glucose- and 3'-deoxy-3'-[18F]fluorothymidine-positron emission tomography as biomarkers of therapy response in platinum-resistant ovarian cancer.
abstract: OBJECTIVE
  We evaluated whether 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) could be used as imaging biomarkers of platinum resensitization in ovarian cancer.
  
  
  METHODS
  Paired platinum-sensitive and platinum-resistant ovarian cancer cells from the same patient, PEO1 and PEO4, grown as tumor xenografts in nude mice, were assessed by PET.
  
  
  RESULTS
  The AKT inhibitor, API-2, resensitized platinum-resistant PEO4 tumors to cisplatin, leading to a markedly lower Ki67 labeling index (p ≤ 0.006, n = 6 per group). [(18)F]FDG-PET and [(18)F]FLT-PET imaging variables were lower after combination treatment compared with vehicle treatment (p ≤ 0.006, n = 6 per group). No changes were seen with either drug alone. PRAS40 phosphorylation status was a sensitive biochemical marker of pathway inhibition, whereas reductions thymidine kinase 1 expression defined the [(18)F]FLT response.
  
  
  CONCLUSIONS
  Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [(18)F]FDG-PET and [(18)F]FLT-PET warranting further assessment.
authors.affiliation: Comprehensive Cancer Imaging Centre, Department of Cancer & Surgery, Faculty of Medicine, Imperial College London, Hammersmith Hospital, 240 MRC Cyclotron Building, Du Cane Road, London, W12 0NN, UK.
authors.forename: Meg
authors.initials: M
authors.lastname: Perumal
authors.forename: Euan A
authors.initials: EA
authors.lastname: Stronach
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002747:Chlorpropamide / Q000031:analogs & derivatives; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D010984:Platinum / Q000494:pharmacology / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D013997:Time Factors; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D000096926:Benzenesulfonamides
chemical_list: D014408:Biomarkers, Tumor; D002747:Chlorpropamide; D015224:Dideoxynucleosides; D019788:Fluorodeoxyglucose F18; D019394:Ki-67 Antigen; D010984:Platinum; C111224:API 2; D000096926:Benzenesulfonamides; C002854:alovudine