Small Animal PET Imaging with 124IFIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model.
- Author:
Min Jeong CHAE
1
;
Tae Sup LEE
;
June Youp KIM
;
Gwang Sun WOO
;
Wee Sup JUMG
;
Kwon Soo CHUN
;
Jae Hong KIM
;
Ji Sup LEE
;
Jin Sook RYU
;
Gi Jeong CHEON
;
Chang Woon CHOI
;
Sang Moo LIM
Author Information
1. Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. larry@kcch.re.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
FIAU;
HSV1-tk;
Small animal PET;
HCC
- MeSH:
Animals;
Arabinofuranosyluracil;
Carcinoma, Hepatocellular;
Cell Count;
Cell Line;
Genes, Reporter;
Genetic Therapy;
Herpes Simplex;
Herpesvirus 1, Human;
Humans;
Liver;
Liver Neoplasms, Experimental;
Methylmethacrylates;
Mice;
Polystyrenes;
Simplexvirus;
Statistics as Topic;
Uracil;
Ursidae
- From:Nuclear Medicine and Molecular Imaging
2008;42(3):235-234
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the develoopement of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-beta-D-arabino-furanosyl-5-[124/125I]iodo- uracil ([124/125I]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. MATERIAL AND METHODS: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [125I]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [124I]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. RESULTS: Specific accumulation of [125I]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [125I]FIAU uptake was linearly correlated (R2=0.964, p=0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [125I]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small aninal PET, [124I]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. CONCLUSION: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.
