title: Combined radionuclide-chemotherapy and in vivo imaging of hepatocellular carcinoma cells after transfection of a triple-gene construct, NIS, HSV1-sr39tk, and EGFP.
abstract: The sodium iodine symporter (NIS) or mutant Herpes-simplex virus type1 sr39 thymidine kinase (HSV1-sr39tk) gene is used for in vivo imaging and cancer therapy. Transfection of both NIS and HSV1-sr39tk genes to hepatocellular carcinoma cells (Huh-7/NTG) could enhance intracellular accumulation of therapeutic radionuclides and guanosine nucleoside analogue prodrugs to produce better outcomes than single gene therapy. Non-invasive imaging with I-124, F-18 FHBG and combination therapy with I-131 and GCV were performed in hepatocellular carcinoma cells transfected with NIS, HSV1-sr39tk and GFP. Our results show that: (1) all three genes are stably expressed in Huh-7/NTG cells, (2) I-125 and H3-PCV uptake were markedly increased in the Huh-7/NTG cells in vitro, (3) cellular survival and tumor growth of Huh-7/NTG was inhibited by I-131 or GCV both in vitro and in vivo, and was much prominent with combination therapy, (4) in vivo imaging with I-124 and F-18 FHBG revealed increased uptake in the Huh-7/NTG tumor. Our results demonstrated the potential of combination gene therapy using NIS and HSV1-sr39tk followed by radioiodine treatment and chemotherapy in human hepatocellular carcinoma cells.
authors.affiliation: Department of Nuclear Medicine and Pharmacology, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: You La
authors.initials: YL
authors.lastname: Lee
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sohn Joo
authors.initials: SJ
authors.lastname: Ahn
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Choi
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Moon
authors.forename: Gi Jeong
authors.initials: GJ
authors.lastname: Cheon
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Lee
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Ahn
authors.forename: Jeoung-Hee
authors.initials: JH
authors.lastname: Ha
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D011355:Prodrugs / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000235:genetics; D027981:Symporters / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D049452:Green Fluorescent Proteins; D007457:Iodine Radioisotopes; D011355:Prodrugs; D019275:Radiopharmaceuticals; D027981:Symporters; D013937:Thymidine Kinase; D000099209:Sodium-Iodide Symporters; C485184:enhanced green fluorescent protein