title: Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice.
abstract: BACKGROUND
  3'-Deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use (18)F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of the experimental chemotherapy Top216 non-invasively by PET.
  
  
  RESULTS
  In vivo uptake of (18)F-FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after Top216 treatment (50 mg/kg i.v. at 0 and 48 hours) was initiated. Baseline (18)F-FLT scans were made before either Top216 (n = 7-10) or vehicle (n = 5-7) was injected and repeated after 2 and 6 hours and 1 and 5 days of treatment. A parallel study was made with 2'-deoxy-2'-[(18)F]fluoro-D-glucose ((18)F-FDG) (n = 8). Tracer uptake was quantified using small animal PET/CT. Imaging results were validated by tumor volume changes and gene-expression of Ki67 and TK1. Top216 (50 mg/kg 0 and 48 hours) inhibited the growth of the A2780 tumor compared to the control group (P<0.001). (18)F-FLT uptake decreased significantly at 2 hours (-52%; P<0.001), 6 hours (-49%; P = 0.002) and Day 1 (-47%; P<0.001) after Top216 treatment. At Day 5 (18)F-FLT uptake was comparable to uptake in the control group. Uptake of (18)F-FLT was unchanged in the control group during the experiment. In the treatment group, uptake of (18)F-FDG was significantly decreased at 6 hours (-21%; P = 0.003), Day 1 (-29%; P<0.001) and Day 5 (-19%; P = 0.05) compared to baseline.
  
  
  CONCLUSIONS
  One injection with Top216 initiated a fast and significant decrease in cell-proliferation assessable by (18)F-FLT after 2 hours. The early reductions in tumor cell proliferation preceded changes in tumor size. Our data indicate that (18)F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients.
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. mettemj@sund.ku.dk
authors.forename: Mette Munk
authors.initials: MM
authors.lastname: Jensen
authors.forename: Kamille Dumong
authors.initials: KD
authors.lastname: Erichsen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Björkling
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.forename: Peter Buhl
authors.initials: PB
authors.lastname: Jensen
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.forename: Maxwell
authors.initials: M
authors.lastname: Sehested
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D015224:Dideoxynucleosides; D004195:Disease Models, Animal; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000503:physiopathology; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D019275:Radiopharmaceuticals; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C002854:alovudine