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: Ju Hui Park, Kwang Il Kim, Kyo Chul Lee, Yong Jin Lee, Tae Sup Lee, Wee Sup Chung, Sang Moo Lim, Joo Hyun Kang
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 30 Issue 1 Pg. 8-15 (Feb 2015) ISSN: 1557-8852 [Electronic] United States
• PMID: 25545853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• alpha-Fetoproteins
• Thymidine Kinase

Topics

• Animals
• Carcinoma, Hepatocellular (diagnostic imaging, genetics, virology)
• Cell Line, Tumor
• Female
• HT29 Cells
• Hep G2 Cells
• Herpesvirus 1, Human (enzymology, genetics)
• Humans
• Liver Neoplasms (diagnostic imaging, genetics, metabolism, virology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Positron-Emission Tomography
• Promoter Regions, Genetic
• Thymidine Kinase (biosynthesis, genetics, metabolism)
• alpha-Fetoproteins (biosynthesis, genetics)