title: The limitation of PET imaging for biological adaptive-IMRT assessed in animal models.
abstract: OBJECTIVE
  Biological image-guided radiotherapy aims at specifically irradiating biologically relevant sub-volumes within the tumor, as determined for instance by PET imaging. This approach requires that PET imaging be sensitive and specific enough to image various biological pathways of interest, e.g. tumor metabolism, proliferation and hypoxia. In this framework, a validation of PET imaging used for adaptive radiotherapy was undertaken in animal models by comparing small-animal PET images (2.7mm resolution) with autoradiography (AR) (100mum resolution) in various tumors under various physiological situations.
  
  
  METHODS
  A specific template for tumor-bearing mouse imaging has been designed (Christian, R&O, 2008). It allows for the registration between MRI images (Biospec, Bruker), FDG-PET images (Mosaic, Philips) and AR (FLA-5100, Fujifilm). After registration, the tumors on the PET and AR images were segmented using a threshold-based method. The thresholds were selected to obtain absolute equal volumes in the PET and AR images. Matching indexes were then calculated between the various volumes. The entire imaging process was performed for FSAII tumors (n=5), SCCVII (n=5) and irradiated (35Gy) FSAII tumors (n=5).
  
  
  RESULTS
  In regions with high FDG activity delineated using high value thresholds, low matching values of 39%+/-11% (mean+/-SD) were observed between the volumes delineated on the PET images and those delineated on AR. The matching values progressively increased when considering larger volumes obtained with lower thresholds. These findings were independent of tumor type, tumor metabolism or tumor size. The relationship between the matching values and the percentage of overall tumor volume was fitted through a power regression (r=0.93). As shown by simulations, the matching improved with higher PET resolution. The results can be extrapolated to human tumors imaged with a whole-body PET system.
  
  
  CONCLUSIONS
  Discrepancies were found between the PET images and the underlying microscopic reality represented by AR images. These differences, attributed to the finite resolution of PET, were important when considering small and highly active regions of the tumors. Dose painting based on PET images should therefore be carefully considered and should take these limitations into account.
authors.affiliation: Center for Molecular Imaging and Experimental Radiotherapy, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Christian
authors.forename: John A
authors.initials: JA
authors.lastname: Lee
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.forename: Marc
authors.initials: M
authors.lastname: De Bast
authors.forename: B
authors.initials: B
authors.lastname: Jordan
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
mesh_terms: D000818:Animals; D001345:Autoradiography; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D019788:Fluorodeoxyglucose F18; D007091:Image Processing, Computer-Assisted; D051379:Mice; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18