title: Evaluation of the specificity of [(18)F]fludarabine PET/CT in a xenograft model of follicular lymphoma: comparison with [(18)F]FDG and impact of rituximab therapy.
abstract: BACKGROUND
  [(18)F]Fludarabine is a novel positron emission tomography (PET) radiotracer for imaging lymphoma. The purpose of this preclinical study was to evaluate the robustness of [(18)F]fludarabine during rituximab therapy. In addition, a comparison was made between [(18)F]fludarabine and [(18)F]fluorodeoxyglucose ([(18)F]FDG) with regard to their concordance with histologically derived data.
  
  
  METHODS
  CB17-SCID mice bearing human follicular DOHH-2 lymphoma were treated once weekly with rituximab (10 mg/kg) or physiological saline over 3 weeks. To obtain the tracer uptake in the metabolically active volume of the tumour (MAVT), a background-level threshold was applied to the volume of interest (VOI) defined on computed tomography (CT) image. The tumour uptake analysis was performed with MAVT-based segmentation for data analysis of sequential [(18)F]fludarabine PET/CT studies and with total tumour-based segmentation for comparison with histologically derived data.
  
  
  RESULTS
  The correlation between the MAVT and [(18)F]fludarabine accumulation (%ID) in those viable tissues was equally significant for both vehicle- or rituximab-treated mice; for these latter, the presence of lymphoid tissues at the end of imaging sessions was confirmed histologically. A stronger correlation was demonstrated between quantitative values extracted from [(18)F]fludarabine-PET and histology (r (2) = 0.91, p < 0.001) when compared to [(18)F]FDG-PET (r (2) = 0.55, p = 0.03).
  
  
  CONCLUSIONS
  [(18)F]Fludarabine uptake in the follicular lymphoma model compared favourably with [(18)F]FDG in terms of specificity for PET imaging and also remained robust for persistent viable tissues following rituximab therapy. [(18)F]Fludarabine PET/CT may be a promising approach to evaluate lymphoma, including their surveillance during therapy.
authors.affiliation: CEA, DSV/I2BM, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France ; Université de Caen Basse-Normandie, Esplanade de la Paix, 14032 Caen, France ; CNRS, UMR ISTCT 6301, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France.
authors.forename: Narinée
authors.initials: N
authors.lastname: Hovhannisyan
authors.affiliation: CEA, DSV/I2BM, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France ; Université de Caen Basse-Normandie, Esplanade de la Paix, 14032 Caen, France ; CNRS, UMR ISTCT 6301, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Guillouet
authors.affiliation: CEA, DSV/I2BM, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France ; Université de Caen Basse-Normandie, Esplanade de la Paix, 14032 Caen, France ; CNRS, UMR ISTCT 6301, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Fillesoye
authors.affiliation: CEA, DSV/I2BM, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France ; Université de Caen Basse-Normandie, Esplanade de la Paix, 14032 Caen, France ; CNRS, UMR ISTCT 6301, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France.
authors.forename: Martine
authors.initials: M
authors.lastname: Dhilly
authors.affiliation: CEA, DSV/I2BM, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France ; Université de Caen Basse-Normandie, Esplanade de la Paix, 14032 Caen, France ; CNRS, UMR ISTCT 6301, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Patin
authors.affiliation: CHU de Caen, Service d'Anatomie Pathologique, Av. de la Côte de Nacre, BP 95182, 14033 Caen, Cedex France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Galateau
authors.affiliation: CEA, DSV/I2BM, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France ; Université de Caen Basse-Normandie, Esplanade de la Paix, 14032 Caen, France ; CNRS, UMR ISTCT 6301, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France.
authors.forename: Michel
authors.initials: M
authors.lastname: Leporrier
authors.affiliation: CEA, DSV/I2BM, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France ; Université de Caen Basse-Normandie, Esplanade de la Paix, 14032 Caen, France ; CNRS, UMR ISTCT 6301, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France.
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
keywords: Imaging; Lymphoma; PET/CT; Rituximab; [18F]Fludarabine