title: Molecular imaging of therapy response with (18)F-FLT and (18)F-FDG following cyclophosphamide and mTOR inhibition.
abstract: OBJECTIVE
  Evaluation and comparison of 3'-[(18)F]-fluoro-3'-deoxy-L-thymidine (FLT) and 2-[(18)F]-fluoro-2-deoxyglucose (FDG)-PET to monitor early response following both cyclophosphamide and temsirolimus treatment in a mouse model of Burkitt lymphoma.
  
  
  METHODS
  Daudi xenograft mice were treated with either cyclophosphamide or temsirolimus and imaged with FLT-PET and FDG-PET on appropriate days post therapy inititiation. Immunohistochemical (IHC) studies (H&E, TUNEL, CD20, PCNA and ki-67) and DNA flow cytometry studies were performed.
  
  
  RESULTS
  FDG tumor uptake decreased immediately after cyclophosphamide treatment while FLT-PET showed only a late and less pronounced decrease. A fast induction of apoptosis was observed together with an early accumulation of cells in the S-phase of the cell cycle, suggesting DNA repair. Temsirolimus treatment reduced both FDG and FLT tumor uptake immediately after therapy and resulted in a fast induction of apoptosis and G(0)-G(1) phase accumulation.
  
  
  CONCLUSIONS
  FLT response was less distinct than FDG response and may be controlled by DNA repair early after cyclophosphamide. Nevertheless, FLT-PET was able to reflect decreased proliferation following temsirolimus.
authors.affiliation: Department of Nuclear Medicine, Maastricht University Medical Centre Maastricht, The Netherlands.
authors.forename: Marijke De
authors.initials: MD
authors.lastname: Saint-Hubert
authors.forename: Lieselot
authors.initials: L
authors.lastname: Brepoels
authors.forename: Ellen
authors.initials: E
authors.lastname: Devos
authors.forename: Peter
authors.initials: P
authors.lastname: Vermaelen
authors.forename: Tjibe De
authors.initials: TD
authors.lastname: Groot
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.forename: Luc
authors.initials: L
authors.lastname: Mortelmans
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
keywords: Burkitt lymphoma; FDG-PET; FLT-PET; cyclophosphamide; mTOR inhibition; therapy response