title: Imaging of treatment response to the combination of carboplatin and paclitaxel in human ovarian cancer xenograft tumors in mice using FDG and FLT PET.
abstract: BACKGROUND
  A combination of carboplatin and paclitaxel is often used as first line chemotherapy for treatment of ovarian cancer. Therefore the use of imaging biomarkers early after initiation of treatment to determine treatment sensitivity would be valuable in order to identify responders from non-responders. In this study we describe the non-invasive PET imaging of glucose uptake and cell proliferation using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) for early assessment of treatment response in a pre-clinical mouse model of human ovarian cancer treated with carboplatin and paclitaxel.
  
  
  METHODS
  In vivo uptake of FLT and FDG in human ovarian cancer xenografts in mice (A2780) was determined before treatment with carboplatin and paclitaxel (CaP) and repeated day 1, 4 and 8 after treatment start. Tracer uptake was quantified using small animal PET/CT. Tracer uptake was compared with gene expression of Ki67, TK1, GLUT1, HK1 and HK2.
  
  
  RESULTS
  Tumors in the CaP group was significantly smaller than in the control group (p=0.03) on day 8. On day 4 FDG SUVmax ratio was significantly lower in the CaP group compared to the control group (105 ± 4% vs 138 ± 9%; p=0.002) and on day 8 the FDG SUVmax ratio was lower in the CaP compared to the control group (125 ± 13% vs 167 ± 13%; p=0.05). On day 1 the uptake of FLT SUVmax ratio was 89 ± 9% in the CaP group and 109 ± 6% in the control group; however the difference was not statistically significant (p=0.08).
  
  
  CONCLUSIONS
  Our data suggest that both FDG and FLT PET may be used for the assessment of anti-tumor effects of a combination of carboplatin and paclitaxel in the treatment of ovarian cancer. FLT provides an early and transient signal and FDG a later and more prolonged response. This underscores the importance of optimal timing between treatment and FLT or FDG imaging since treatment response may otherwise be overlooked.
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark ; Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Munk Jensen
authors.affiliation: Topotarget A/S, Copenhagen, Denmark.
authors.forename: Kamille Dumong
authors.initials: KD
authors.lastname: Erichsen
authors.affiliation: Topotarget A/S, Copenhagen, Denmark ; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Björkling
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.affiliation: Topotarget A/S, Copenhagen, Denmark.
authors.forename: Peter Buhl
authors.initials: PB
authors.lastname: Jensen
authors.affiliation: Topotarget A/S, Copenhagen, Denmark.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Sehested
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark ; Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark ; Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D016190:Carboplatin; D017239:Paclitaxel