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Small Animal PET Imaging with [$^{124}I$]FIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model  

Chae, Min-Jeong (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences)
Lee, Tae-Sup (Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences)
Kim, June-Youp (Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences)
Woo, Gwang-Sun (Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences)
Jumg, Wee-Sup (Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences)
Chun, Kwon-Soo (Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences)
Kim, Jae-Hong (Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences)
Lee, Ji-Sup (Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences)
Ryu, Jin-Sook (Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine)
Cheon, Gi-Jeong (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences)
Choi, Chang-Woon (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences)
Lim, Sang-Moo (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences)
Publication Information
Nuclear Medicine and Molecular Imaging / v.42, no.3, 2008 , pp. 235-245 More about this Journal
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 development 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-furanosyi-5-[$^{124/125}I$]iodo- uracil ([$I^{124/125}I$]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 [$^{125}I$]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [$^{124}I$]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. Results:, Specific accumulation of [[$^{125}I$]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. [$^{125}I$]FIAU uptake was linearly correlated (R2 =0.964, p =0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [$^{125}I$]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 animal PET, [$^{124}I$]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.
Keywords
FIAU; HSV1-tk; Small animal PET; HCC;
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1 Qian C, Idoate M, Bilbao R, Sangro B, Bruna O, Vazquez J, et al. Gene transfer and therapy with adenoviral vector in rats with diethylnitrosamine-induced hepatocellular carcinoma. Hum Gene Ther 1997:8:349-58   DOI   ScienceOn
2 Bilbao R, Gerolami R, Bralet MP, Qian C, Tran PL, Tennant B, et al. Transduction efficacy, antitumoral effect and toxicity of adenovirusmediated herpes simplex virus thymidine kinase/ganciclovir therapy of hepatocellular carcinoma: The woodchuck animal model. Cancer Gene Ther 2000;7:657-62   DOI
3 Miyagawa M, Anton M, Haubner R, Simoes MV, Stadele C, Erhardt W. et al. PET of cardiac transgene expression: comparison of 2 approaches based on herpesviral thymidine kinase reporter gene. J Nucl Med 2004;45:1917-23
4 Morin KW, Atrazheva ED, Knaus EE, Wiebe LI. Synthesis and cellular uptake of 2-substituted analogues of (E)-5-(2-$[^{125}I]$ iodovinyl)-2_-deoxyuridine in tumor cells transduced with the herpes simplex type-1 thymidine kinase gene: evaluation as probes for monitoring gene therapy. J Med. Chem 1997;40: 2184-90   DOI   ScienceOn
5 Gambhir SS, Bauer E, Black ME, Liang Q, Kokoris MS, Barrio JR, et al. A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography. Proc. Natl. Acad. Sci. USA 2000;97:2785-90   DOI
6 Tjuvajev JG, Doubrovin M, Akhurst T, Cai S, Balatoni J, Alauddin MM, et al. Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression. J Nucl Med 2002;43:1072-83
7 Haberkorn U, Altmann A, Morr I, Knopf KW, Germann C, Haeckel R, et al. Monitoring gene therapy with herpes simplex virus thymidine kinase in hepatoma cells: uptake of specific substrates. J Nucl Med 1997;38:287-294
8 Haubner R, Avril1 N, Hantzopoulos PA, Gansbacher B, Schwaiger M. In vivo imaging of herpes simplex virus type 1 thymidine kinase gene expression: early kinetics of radiolabelled FIAU. Eur J Nucl Med 2000; 27:283-91   DOI
9 Moon BS, Lee TS, Lee MK, Lee KC, An GI, Chun KS, et al. Synthesis and Preliminary Evaluation of 9-(4-$[^{18}F]$Fluoro-3-hydroxymethylbutyl) Guanine ($[^{18}F]$FHBG) in HSV1-tk Gene Transduced Hepatoma Cell. Nucl Med Mol Imaging 2006;4:218-27   과학기술학회마을
10 Namavari M, Barrio JR, Toyokuni T, Gambhir SS, Cherry SR, Herschman HR, et al. Synthesis of 8-$[^{18}F]$fluoroguanine derivatives: in vivo probes for imaging gene expression with positron emission tomography. Nucl. Med. Biol 2000;27:157-62   DOI   ScienceOn
11 Beck C, Cayeux S, Lupton SD, Dorken B, Blankenstein T. The thymidine kinase/ganciclovir-mediated "suicide" effect is variable in different tumor cells. Hum Gene Ther 1995;6:1525-1530   DOI   ScienceOn
12 Brust P, Haubner R, Friedrich A, Scheunemann M, Anton M, Koufaki ON, et al. Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene xpression. J Nucl Med 2001;28:721-9   DOI   ScienceOn
13 Alauddin MM, Conti PS, Mazza SM, Hamzeh FM, Lever JR. 9 - [ ( 3-$[^{18}F]$-Fluoro-1-hydroxy-2-propoxy)methyl]guanine ($[^{18}F]$-FHPG): a potential imaging agent of viral infection and gene therapy using PET. Nucl. Med. Biol 1996;23:787-92   DOI   ScienceOn
14 Tovell DR, Samuel J, Mercer JR, Misra HK, Xu L, Wiebe LI, et al. The in vitro evaluation of nucleoside analogues as probes for use in the noninvasive diagnosis of herpes simplex encephalitis. Drug Des. Deliv 1988;3:213-21
15 Kang KW, Min JJ, Chen X, Gambhir SS. Comparison of [14C]FMAU, [3H]FEAU, [14C]FIAU, and [3H]PCV for monitoring reporter gene expression of wild type and mutant herpes simplex virus type 1 thymidine kinase in cell culture. Mol Imaging Biol 2005 7:296-303   DOI
16 Elion GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ. Selectivity of action of an antiherpetic agent, 9-(2- hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A 1977; 74:5716-20   DOI   ScienceOn
17 Min JJ, Iyer M, Gambhir SS. Comparison of [18F]FHBG and [14C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection..Eur J Nucl Med Mol Imaging 2003;30(11):1547-60   DOI
18 Juan Ruiz, Guillermo Mazzolini, Bruno Sangro, Cheng Qian, Jesus Prieto. Gene Therapy of Hepatocellular Carcinoma. Dig Dis 2001; 19:324-32   DOI   ScienceOn
19 Martin JA, Thomas GJ, Merrett JH, Lambert RW, Bushnell DJ, Dunsdon SJ, et al. The design, synthesis and properties of highly potent and selective inhibitors of herpes simplex virus types 1 and 2 thymidine kinase. Antivir Chem Chemother 1998;9:1-8   DOI
20 Gerolami R, Cardoso J, Lewin M, Bralet MP, Sa Cunha A, Clement O, et al. Evaluation of HSV-tk gene therapy in a rat model of chemically induced hepatocellular carcinoma by intratumoral and intrahepatic artery routes. Cancer Res 2000:60:993-1001
21 Alauddin MM, Conti PS. Synthesis and preliminary evaluation of 9-(4-$[^{18}F]$-fluoro -3-hydroxymethylbutyl)guanine ($[^{18}F]$FHBG): a new potential imaging agent for viral infection and gene therapy using PET. Nucl. Med. Biol 1998;25:175-80   DOI   ScienceOn
22 Morin KW, Duan W, Xu L, Zhou A, Moharram S, Knaus EE. et al. Cytotoxicity and cellular uptake of pyrimidine nucleosides for imaging herpes simplex type-1 thymidine kinase (HSV-1 TK) expression in mammalian cells. Nucl Med Biol 2004;31:623-30   DOI   ScienceOn
23 Chia-Hung Hsieha, Ren-Shyan Liua,b, Hsin-Ell Wang. In vitro evaluation of herpes simplex virus type 1 thymidine kinase reporter system in dynamic studies of transcriptional gene regulation Nucl Med Biol 33 (2006) 653-60
24 Cheng YC, Huang ES, Lin JC, Mar EC, Pagano JS, Dutschman GE, et al. Unique spectrum of activity of 9-[(1,3-dihydroxy-2- propoxy)-methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1. Proc Natl Acad Sci U S A 1983;80:2767-70   DOI   ScienceOn
25 Tjuvajev JG, Stockhammer G, Desai R, Uehara H, Watanabe K, Gansbacher B, et al. Imaging the expression of transfected genes in vivo. Cancer Res 1995;55:6126-32
26 Min JJ, Iyer M, Gambhir SS. Comparison of $^{18}F$-FHBG and $^{14}C$-FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection. Eur J Nucl Med Mol Imaging 2003;30:1547-60   DOI
27 Keller PM, Fyfe JA, Beauchamp L, Lubbers CM, Furman PA, Schaeffer HJ, et al. Enzymatic phosphorylation of acyclic nucleoside analogs and correlations with antiherpetic activities. Biochem Pharmacol 1981;30:3071-7   DOI   ScienceOn
28 de Vries EF, van Waarde A, Harmsen MC, Mulder NH, Vaalburg W, Hospers GA. $[^{11}C]$FMAU and $[^{18}F]$FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections. Nucl. Med. Biol. 2000;27:113-9   DOI   ScienceOn