title: Tumour microenvironment heterogeneity affects the perceived spatial concordance between the intratumoural patterns of cell proliferation and 18F-fluorothymidine uptake.
abstract: OBJECTIVE
  PET imaging with (18)F-fluorothymidine ((18)F-FLT) can potentially be used to identify tumour subvolumes for selective dose escalation in radiation therapy. The purpose of this study is to analyse the co-localization of intratumoural patterns of cell proliferation with (18)F-FLT tracer uptake.
  
  
  METHODS
  Mice bearing FaDu or SQ20B xenograft tumours were injected with (18)F-FLT, and bromodeoxyuridine (proliferation marker). Ex vivo images of the spatial pattern of intratumoural (18)F-FLT uptake and that of bromodeoxyuridine DNA incorporation were obtained from thin tumour tissue sections. These images were segmented by thresholding and Relative Operating Characteristic (ROC) curves and Dice similarity indices were evaluated.
  
  
  RESULTS
  The thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation were significantly different for the two xenograft tumour models, whereas the median Dice values were not. However, ROC analysis indicated that segmented FLT images were more specific at detecting the proliferation pattern in FaDu tumours than in SQ20B tumours.
  
  
  CONCLUSIONS
  Highly dispersed patterns of cell proliferation observed in certain tumours can affect the perceived spatial concordance between the spatial pattern of (18)F-FLT uptake and that of cell proliferation even when high-resolution ex vivo autoradiography imaging is used for (18)F-FLT imaging.
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0037, USA.
authors.forename: Marian
authors.initials: M
authors.lastname: Axente
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Bass
authors.forename: Jerry I
authors.initials: JI
authors.lastname: Hirsch
authors.forename: Gobalakrishnan
authors.initials: G
authors.lastname: Sundaresan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Williamson
authors.forename: Jamal
authors.initials: J
authors.lastname: Zweit
authors.forename: Andrei
authors.initials: A
authors.lastname: Pugachev
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology*; D049268:Positron-Emission Tomography; D012372:ROC Curve; D019275:Radiopharmaceuticals; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D001973:Bromodeoxyuridine