title: Intra-tumoral distribution of (64)Cu-ATSM: a comparison study with FDG.
abstract: (64)Cu-labeled diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) is a promising agent for internal radiation therapy and imaging of hypoxic tissues. In the present study, the intra-tumoral distribution of (64)Cu-ATSM was investigated by comparing it to that of [(18)F]FDG and histological findings. VX2 tumors were implanted into Japanese white rabbits subcutaneously. (64)Cu-ATSM and [(18)F]FDG were co-injected intravenously and the tumor was dissected and cut into 1 mm thick slices 1 h after the injection. The uptake of (64)Cu-ATSM and [(18)F]FDG was measured using a dual-tracer autoradiographic technique. Histological cell biology was estimated from the optical microscopy of tumor sections. The major accumulation of (64)Cu-ATSM was observed around the outer rim of the tumor masses which consisted mainly of active cells and expected to be hypoxic. [(18)F]FDG was distributed more widely with highest levels in the inner regions where pre-necrotic cells were mainly observed. (64)Cu-ATSM appears to be useful for the detection of hypoxic but active tumor cell regions in vivo.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, 606-8151 Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Obata
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Shingo
authors.initials: S
authors.lastname: Kasamatsu
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
authors.forename: Shinji
authors.initials: S
authors.lastname: Takamatsu
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kashikura
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Yonekura
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujibayashi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056831:Coordination Complexes; D003301:Copper Radioisotopes / Q000493:pharmacokinetics*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013882:Thiosemicarbazones / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); D019788:Fluorodeoxyglucose F18