title: Monitoring tumor response with radiolabeled nucleoside analogs in a hepatoma-bearing mouse model early after doxisome(®) treatment.
abstract: OBJECTIVE
  This study aims to demonstrate that 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) positron emission tomography (PET) is a promising modality for noninvasively monitoring the therapeutic efficacy of Doxisome(®) in a subcutaneous hepatoma mouse model.
  
  
  METHODS
  Male BALB/c nu/nu mice were inoculated with HepG2 hepatoma xenograft in the right flank. Doxisome(®) (5 mg/kg, three times a week for 2 weeks) was intravenously administrated for treatment. (18)F-FLT-microPET, biodistribution studies, and immunohistochemistry of Ki-67 were performed.
  
  
  RESULTS
  A significant difference (p < 0.05) in tumor volume was observed on day 5 between treated and control groups. The tumor-to-muscle ratio derived from (18)F-FLT-PET and (123)I-ICdR-microSPECT images of Doxisome(®)-treated mice dropped from 12.55 ± 0.76 to 3.81 ± 0.31 and from 2.48 ± 0.42 to 1.59 ± 0.08 after a three-dose treatment, respectively, while that of the control group remained steady. The retarded proliferation rate of treated xenograft was confirmed by Ki-67 immunohistochemistry staining.
  
  
  CONCLUSIONS
  This study clearly demonstrated that Doxisome(®) is an effective anti-cancer drug against the growth of HepG2 hepatoma and that (18)F-FLT-PET could provide early information of tumor response during treatment.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No.155, Sec.2, Li-Nong St., Taipei, Taiwan 11217.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Lin-Shan
authors.initials: LS
authors.lastname: Chou
authors.forename: Pei-Chia
authors.initials: PC
authors.lastname: Chan
authors.forename: Chung-Hsien
authors.initials: CH
authors.lastname: Ho
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Lin
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Shen
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
mesh_terms: D000818:Animals; D001972:Bromodeoxycytidine / Q000031:analogs & derivatives; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D015224:Dideoxynucleosides; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004705:Endocytosis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D064847:Multimodal Imaging; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D049268:Positron-Emission Tomography; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; C506643:liposomal doxorubicin; D003841:Deoxycytidine; D001972:Bromodeoxycytidine; C011288:ibacitabine; D011092:Polyethylene Glycols; D004317:Doxorubicin; C002854:alovudine