title: Assessment of α-fetoprotein targeted HSV1-tk expression in hepatocellular carcinoma with in vivo imaging.
abstract: Tumor-specific enhancer/promoter is applicable for targeting gene expression in tumors and helpful for tumor-targeting imaging and therapy. We aimed to acquire α-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) specific images using adenovirus containing HSV1-tk gene controlled by AFP enhancer/promoter and evaluate in vivo ganciclovir (GCV)-medicated therapeutic effects on AFP-targeted HSV1-tk expression with (18)F-FDG positron emission tomography (PET). Recombinant adenovirus expressing HSV1-tk under AFP enhancer/promoter was produced (AdAFP-TK) and the expression levels were evaluated by RT-PCR and (125)I-IVDU uptake. GCV-mediated HSV1-tk cytotoxicity was determined by MTT assay. After the mixture of AdAFP-fLuc and AdAFP-TK was administrated, bioluminescent images (BLIs) and (18)F-FHBG PET images were obtained in tumor-bearing mice. In vivo therapeutic effects of AdAFP-TK and GCV in the HuH-7 xenograft model were monitored by (18)F-FDG PET. When infected with AdAFP-TK, cell viability in HuH-7 was reduced, but those in HT-29 and SK-Hep-1 were not significantly decreased at any GCV concentration less than 100 μM. AFP-targeted fLuc and HSV1-tk expression were clearly visualized by BLI and (18)F-FHBG PET images in AFP-producing HCC, respectively. In vivo GCV-mediated tumor growth inhibition by AFP-targeted HSV1-tk expression was monitored by (18)F-FDG PET. Recombinant AdAFP-TK could be applied for AFP-targeted HCC gene therapy and imaging in AFP-producing HCC.
authors.affiliation: 1 Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences , Seoul, Republic of Korea.
authors.forename: Ju Hui
authors.initials: JH
authors.lastname: Park
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Tae Sup
authors.initials: TS
authors.lastname: Lee
authors.forename: Wee Sup
authors.initials: WS
authors.lastname: Chung
authors.forename: Sang Moo
authors.initials: SM
authors.lastname: Lim
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000235:genetics* / Q000821:virology; D045744:Cell Line, Tumor; D005260:Female; D019073:HT29 Cells; D056945:Hep G2 Cells; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000509:alpha-Fetoproteins; D013937:Thymidine Kinase
keywords: 18F-FDG PET; 18F-FHBG PET; herpes simplex virus type 1-thymidine kinase; tumor-targeting imaging; α-fetoprotein