title: Comparison of intratumoral FDG and Cu-ATSM distributions in cancer tissue originated spheroid (CTOS) xenografts, a tumor model retaining the original tumor properties.
abstract: BACKGROUND
  The intratumoral distributions of [(18)F]FDG and [(64)Cu]Cu-ATSM have been reported to be similar in adenocarcinomas but different in squamous cell carcinoma (SCC) in clinical studies. In the present study, we compared the intratumoral distributions of these two tracers in cancer tissue originated spheroid (CTOS) xenografts derived from adenocarcinoma and SCC, which retain the histological characteristics of the original tumors, and in cancer cell line xenografts of corresponding origin, to investigate the underlying mechanism of the distinct FDG and Cu-ATSM distribution patterns in adenocarcinoma and SCC.
  
  
  METHODS
  CTOSs derived from colon adenocarcinoma and lung SCC and cell lines established from colon adenocarcinoma and lung SCC, which were used for comparison, were subcutaneously transplanted into immunodeficient mice. One hour after administering [(14)C]FDG and [(64)Cu]Cu-ATSM, the intratumoral distributions were compared in the xenografts by using dual-tracer autoradiography. Adjacent sections were evaluated for necrosis, vasculature anatomy, Ki-67 antigen, and pimonidazole adducts using hematoxylin and eosin and immunohistochemical staining.
  
  
  RESULTS
  There was a higher regional overlap of high FDG and Cu-ATSM accumulations in the adenocarcinoma CTOS xenografts than in the SCC CTOS xenografts, while the overlap in the adenocarcinoma cell line xenograft was lower than that observed in the SCC cell line. High FDG accumulation occurred primarily in proximity to necrotic or pimonidazole adduct positive regions, while high Cu-ATSM accumulation occurred primarily in live cell regions separate from the necrotic regions. The adenocarcinoma CTOS xenograft had the stereotypical glandular structure, resulting in more intricately mixed regions of live and necrotic cells compared to those observed in the SCC CTOS or the cell line xenografts.
  
  
  CONCLUSIONS
  Tumor morphological characteristics, specifically the spatial distribution of live and necrotic cell regions, appeared to be one of the most critical factors determining the regional overlap of FDG and Cu-ATSM distributions in adenocarcinoma.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. Electronic address: tfuru@nirs.go.jp.
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Jin
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Winn
authors.initials: W
authors.lastname: Aung
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yoshii
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Sumitaka
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Endo
authors.affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujibayashi
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000473:pathology; D056831:Coordination Complexes; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D051379:Mice; D009942:Organometallic Compounds / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology*; D013882:Thiosemicarbazones / Q000378:metabolism*
chemical_list: D056831:Coordination Complexes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); D019788:Fluorodeoxyglucose F18
keywords: Adenocarcinoma; Cu-ATSM; FDG; Intratumoral distribution; Squamous cell carcinoma