title: Histopathologic validation of 3'-deoxy-3'-18F-fluorothymidine PET for detecting tumor repopulation during fractionated radiotherapy of human FaDu squamous cell carcinoma in nude mice.
abstract: OBJECTIVE
  FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrates accelerated tumor repopulation during fractionated irradiation with pathological validation (Ki-67 and BrdUrd makers) in a xenograft model system. However, these and other functional assays must be performed ex vivo and post hoc. We propose a novel, in vivo, real-time assay utilizing (18)F-FLT PET.
  
  
  METHODS
  Nude mice with FaDu-hSCC were irradiated with 12 or 18 fractions of 1.8 Gy ([Dm]=3.0 Gy), either daily or every second day. (18)F-FLT micro-PET scans were performed at different time points, FLT parameters (SUVmax, SUVmean, and T/NT) were measured. Tumor sections were stained for Ki-67 and BrdUrd, a labeling index (LI) was calculated. Imaging-pathology correlation was determined by comparing FLT parameters and immunohistochemical results.
  
  
  RESULTS
  Measured SUVmax, SUVmean and T/NT decreased significantly after daily irradiation with 12 fractions in 12 days (P<0.05) and 18 fractions in 18 days (P<0.05). In contrast, these parameters increased in mice treated with 12 fractions in 24 days (P>0.05) and 18 fractions in 36 days (P>0.05), suggesting accelerated repopulation. Similarly, Ki-67 and BrdUrd LIs demonstrated significant decreases with daily irradiation (P<0.05), and increases with every-second-day irradiation (P>0.05). (18)F-FLT parameters correlated strongly with proliferation markers (r(2): 0.679-0.879, P<0.001).
  
  
  CONCLUSIONS
  (18)F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for (18)F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy.
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Jin-Bo
authors.initials: JB
authors.lastname: Yue
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China; Jinan University, Shandong Academy of Medical Sciences, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Graduate Education Center of Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, USA.
authors.forename: Alvin R
authors.initials: AR
authors.lastname: Cabrera
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Xin-Dong
authors.initials: XD
authors.lastname: Sun
authors.affiliation: Department of Radiology, The 2nd Affiliated Hospital of Wenzhou Medical University, China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Bai
authors.affiliation: Department of Pathology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China. Electronic address: sdyujinming@126.com.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yu
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D048708:Cell Growth Processes / Q000502:physiology / Q000528:radiation effects; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides; D019583:Dose Fractionation, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D011897:Random Allocation; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine
keywords: (18)F-fluorothymidine PET; Fractionated radiotherapy; Immunohistochemistry; Proliferation; Tumor repopulation