title: Histopathologic validation of 3'-deoxy-3'-18F-fluorothymidine PET in squamous cell carcinoma of the oral cavity.
abstract: Accelerated tumor cell repopulation is an important mechanism adversely affecting therapeutic outcome in head and neck cancer. The noninvasive assessment of the proliferative state of a tumor by PET may provide a selection tool for customized treatment. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a PET tracer that is phosphorylated by thymidine kinase 1 (TK-1) and, as such, reflects cellular proliferation. Before the use of (18)F-FLT PET for tumor characterization is accepted and introduced into clinical studies, validation against tumor histology is mandatory. The aim of this study was to validate (18)F-FLT PET in squamous cell carcinomas of the oral cavity using immunohistochemical staining for the proliferation marker iododeoxyuridine and for TK-1.
  
  
  METHODS
  Seventeen patients with primary squamous cell carcinomas of the oral cavity underwent an (18)F-FLT PET/CT scan before surgery, and iododeoxyuridine was administered 20 min before tumor resection. (18)F-FLT PET/CT scans were segmented, and PET/CT volumes and PET signal intensities were calculated (mean standardized uptake value [SUV(mean)] and maximum standardized uptake value [SUV(max)]). Multiple paraffin-embedded tumor sections were immunohistochemically stained for iododeoxyuridine and TK-1. For iododeoxyuridine, labeling indices and optical densities were calculated and correlated with SUV(mean) and SUV(max). TK-1 staining was visually and semiquantitatively assessed.
  
  
  RESULTS
  All primary tumors were identified with (18)F-FLT PET but with a large range in tracer uptake (mean SUV(max), 5.9; range, 2.2-15.2). Also, there was a large variability in iododeoxyuridine labeling indices (mean, 0.09; range, 0.01-0.29) and optical densities (mean, 28.2; range, 12.6-37.8). The iododeoxyuridine optical densities correlated significantly with SUV(mean) and SUV(max), but the labeling indices did not. In most tumors, TK-1 staining of varying intensity was present but correlated with neither iododeoxyuridine binding nor (18)F-FLT uptake.
  
  
  CONCLUSIONS
  The current study demonstrated only a weak correlation between (18)F-FLT uptake and iododeoxyuridine staining intensity in oral cavity tumors. This weak correlation may be explained by differences in biomarker characteristics, resolution, and quantification methods.
authors.affiliation: Department of Radiation Oncology, Institute of Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. e.troost@rther.umcn.nl
authors.forename: Esther G C
authors.initials: EG
authors.lastname: Troost
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.forename: Piet J
authors.initials: PJ
authors.lastname: Slootweg
authors.forename: Wenny J M
authors.initials: WJ
authors.lastname: Peeters
authors.forename: Matthias A W
authors.initials: MA
authors.lastname: Merkx
authors.forename: Albert J
authors.initials: AJ
authors.lastname: van der Kogel
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Johannes H A M
authors.initials: JH
authors.lastname: Kaanders
mesh_terms: D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology*; D015224:Dideoxynucleosides; D005260:Female; D006801:Humans; D007065:Idoxuridine; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D013937:Thymidine Kinase / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D015415:Biomarkers; D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D007065:Idoxuridine; C002854:alovudine