bromodeoxycytidine and Liver-Neoplasms

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.. 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.. 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.. 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.

Topics: Animals; Bromodeoxycytidine; Carcinoma, Hepatocellular; Cell Cycle Checkpoints; Cell Death; Deoxycytidine; Dideoxynucleosides; Disease Models, Animal; Doxorubicin; Endocytosis; Hep G2 Cells; Humans; Immunohistochemistry; Ki-67 Antigen; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Multimodal Imaging; Polyethylene Glycols; Positron-Emission Tomography; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Outcome; Xenograft Model Antitumor Assays