title: Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma.
abstract: This study evaluated a multifunctional micelle simultaneously loaded with doxorubicin (Dox) and labeled with radionuclide rhenium-188 ((188)Re) as a combined radiotherapy and chemotherapy treatment for hepatocellular carcinoma. We investigated the single photon emission computed tomography, biodistribution, antitumor efficacy, and pathology of (188)Re-Dox micelles in a murine orthotopic luciferase-transfected BNL tumor cells hepatocellular carcinoma model. The single photon emission computed tomography and computed tomography images showed high radioactivity in the liver and tumor, which was in agreement with the biodistribution measured by γ-counting. In vivo bioluminescence images showed the smallest size tumor (P<0.05) in mice treated with the combined micelles throughout the experimental period. In addition, the combined (188)Re-Dox micelles group had significantly longer survival compared with the control, (188)ReO4 alone (P<0.005), and Dox micelles alone (P<0.01) groups. Pathohistological analysis revealed that tumors treated with (188)Re-Dox micelles had more necrotic features and decreased cell proliferation. Therefore, (188)Re-Dox micelles may enable combined radiotherapy and chemotherapy to maximize the effectiveness of treatment for hepatocellular carcinoma.
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan ; Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: Ying-Hsia
authors.initials: YH
authors.lastname: Shih
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: Cheng-Liang
authors.initials: CL
authors.lastname: Peng
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan ; Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: Ping-Fang
authors.initials: PF
authors.lastname: Chiang
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan ; Institute of Radiological Science, Central University, Taichung, Taiwan.
authors.forename: Tsai-Yueh
authors.initials: TY
authors.lastname: Luo
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan ; Department of Oncology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Jium
authors.initials: MJ
authors.lastname: Shieh
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005260:Female; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D012211:Rhenium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D008823:Micelles; D011108:Polymers; D019275:Radiopharmaceuticals; D012211:Rhenium; D004317:Doxorubicin
keywords: 188Re-Dox micelles; chemotherapeutic; hepatocellular carcinoma; radiotherapeutic