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In Vitro Uptakes of Radiolabeled IVDU and IVFRU in Herpes Simplex Virus Type-1 Thymidine Kinase (HSV1-tk) Gene Transduced Morris Hepatoma Cell Line  

Lee, Tae-Sup (Laboratory of Cyclotron Application, Korea Institute of Radiological and Medical Sciences(KIRAMS))
Choi, Tae-Hyun (Laboratory of Cyclotron Application, Korea Institute of Radiological and Medical Sciences(KIRAMS))
Ahn, Soon-Hyuk (Laboratory of Cyclotron Application, Korea Institute of Radiological and Medical Sciences(KIRAMS))
Woo, Kwang-Sun (Laboratory of Cyclotron Application, Korea Institute of Radiological and Medical Sciences(KIRAMS))
Jeong, Wee-Sup (Laboratory of Cyclotron Application, Korea Institute of Radiological and Medical Sciences(KIRAMS))
Kwon, Hee-Chung (Laboratory of Molecular Oncology, Korea Institute of Radiological and Medical Sciences(KIRAMS))
Awh, Ok-Doo (Department of Medical Laboratory Science, College of Health Science, Yonsei University)
Choi, Chang-Woon (Laboratory of Cyclotron Application, Korea Institute of Radiological and Medical Sciences(KIRAMS))
Lim, Sang-Moo (Laboratory of Cyclotron Application, Korea Institute of Radiological and Medical Sciences(KIRAMS))
Publication Information
The Korean Journal of Nuclear Medicine / v.38, no.1, 2004 , pp. 62-73 More about this Journal
Abstract
Purpose: The herpes simplex virus type 1 thymidine kinase gene(HSV1-tk) is an attractive candidate as a reporter gene in noninvasive reporter gene monitoring system. The HSV1-tk gene was chosen as a reporter gene, because it has been extensively studied, and there are appropriate reporter probes, substrates of HSV1-tk gene product, to apply for HSV1-tk gene imaging. We used radiolabeled 5-iodovinyl-2'-deoxyuridine (IVDU) and 5-iodovinyl-2'-fluoro-2'-deoxyuridine (IVFRU) as reporter probes for HSV1-tk gene monitoring system. Materials and Methods: We prepared HSV1-tk gene transduced Morris hepatoma cell line using retroviral vector, MOLTEN containing HSV1-tk gene. And we confirmed the HSV1-tk gene expression by Northern blotting and Western blotting. We compared in vitro uptakes of radioiodinated IVDU and IVFRU to monitor HSV1-tk gene expression in Morris hepatoma cell line (MCA) and HSV1-tk gene tranduced MCA (MCA-tk) cells until 480 minutes. We also peformed correlation analysis between percentage of HSV1-tk gene tranduced MCA cell % (MCA-tk%) and uptakes of radiolabeled IVDU or IVFRU. Results: MCA-tk cell expressed HSV1-tk mRNA and HSV1-TK protein. Two compounds showed minimal uptake in MCA, but increased uptake was observed in MCA-tk. IVDU showed 4-fold higher accumulation than IVFRU at 480 min in MCA-tk (p<0.01). Both IVDU and IVFRU uptake were linearly correlated ($R^2>0.96$) with increasing MCA-tk%. Conclusion: The radiolabeld IVDU and IVFRU showed higher specific accumulation in retrovirally HSV1-tk gene transfected Morris hepatoma cell line. Both IVDU and IVFRU could be used as good substrates for evaluation of HSV1-tk gene expression.
Keywords
Radiolabeled IVDU and IVFRU; Herpes simplex virus type 1 thymidine kinase(HSV1-tk); Gene imaging; Gene therapy;
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1 Weinberg RA. The retinoblastoma protein and cell cycle control. Cell 1995;81:323-30   DOI   PUBMED   ScienceOn
2 Smee DF, Martin JC, Verheyden JP, Matthews TR. Anti-herpesvirus activity of the acyclic nucleoside 9 - (1,3-dihydroxy-2-propoxymethyl)guanine. Antimicrob Agents Chemother 1983;23:676-682   DOI   PUBMED   ScienceOn
3 Watanabe KA, Reichman U, Hirota K, Lopez C, Fox JJ. Nucleosides. 110. Synthesis and antiherpes virus activity of some 2'-fluoro-2'-deoxyarabinofuran-osylpyrimidine nucleosides. J Med Chem 1979;22:21-24
4 Choi TH, Ahn SH, Choi CW, Lim SM, Awh OD. Synthesis of substrates for gene monitoring of HSV1-tk system. Korean J Nucl Med 2002;36:102-109
5 Brust P, Haubner R, Friedrich A, Scheunemann M, Anton M, Koufaki ON, Hauses M, Noll S, Noll B, Haberkorn U, Schackert G, Schackert HK, Avril N, Johannsen B. Comparison of $[^{18}F]$FHPG and $[^{124}/^{125}I]$FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression. Eur J Nucl Med 2001;28:721-729   DOI   ScienceOn
6 Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994 ;54:4855-4878   PUBMED
7 Alauddin MM, Shahinian A, Gordon EM, Hall FL, Conti PS. Comparative evaluation of FMAU and acycloguanine derivatives, FHPG and FHBG in MDA-MB-468 breast cancer cells for gene therapy imaging [abstract]. J Nucl Med 2002;43(Suppl):275
8 Balzarini J, De Clercq E, Verbruggen A, Ayusawa D, Seno T. Highly selective cytostatic activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine derivatives for murine mammary carcinoma (FM3A) cells transformed with the herpes simplex virus type 1 thymidine kinase gene. Mol Pharmacol 1985;28:581-587   PUBMED
9 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 2003;30:1547-1560   DOI
10 Zinn KR, Chaudhuri TR, Buchsbaum DJ, Mountz JM, Rogers BE. Simultaneous evaluation of dual gene transfer to adherent cells by gamma-ray imaging. Nucl Med Biol 2001;28:135-144   DOI   ScienceOn
11 Wang HE, Deng WP, Chang PF, Chang CW, Liu RS, Lin WJ, Ting G.. Evaluation and comparison $of^{18}F-FHBG and ^{131}$I-FIAU as gene probes in gene therapy [abstract]. J Nucl Med 2002;43(Suppl):274
12 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 USA 1977;74:5716-5720   DOI   ScienceOn
13 De Clercq E, Descamps J, Balzarini J, Fukui T, Allaudeen HS. Antiviral activity of the 3'-amino derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine. Biochem J 1983;211(2):439-45   DOI   PUBMED
14 Tjuvajev JG, Stockhammer G, Desai R, Uehara H, Watanabe K, Gansbacher B, Blasberg RG. Imaging the expression of transfected genes in vivo. Cancer Res 1995;55:6126-6132   PUBMED
15 Tjuvajev JG, Doubrovin M, Akhurst T, Cai S, Balatoni J, Alauddin MM, Finn R, Bornmann W, Thaler H, Conti PS, Blasberg RG.. Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression. J Nucl Med 2002;43:1072-1083   PUBMED
16 Freeman SM, Whartenby KA, Freeman JL, Abboud CN, Marrogi AJ. In situ use of suicide genes for cancer therapy. Semin Oncol 1996;23(1):31-45   PUBMED
17 Abrams DN, Lee YW, Mercer JR, KnausEE, Wiebe LI. Tumor uptake of radiolabeled pyrimidine bases and pyrimidine nucleosides in animal models. IX. Radiolabeled 1-(2-fluoro-2-deoxy-$\beta$-D-ribofuranosyl)uracil and 1-(2-chloro-2-deoxy-$\beta$-D- ribofuranosyl) uracil. Br J Radiol 1986;59:263-268.
18 Balzarini L, Morin KW, Kanus EE, Wiebe LI, De Clercq E. Novel (E)-5-(2-iodovinyl)-2-deoxyuridine derivatives as potential cytostatic agents against herpes simplex virus thymidine kinase gene transfected tumors. Gene Ther 1995;2:317-322   DOI
19 Culver KW, Blaese RM. Gene therapy for cancer. Trends Genet 1994;10:174-178 12. Culver KW, Blaese RM. Gene therapy for cancer. Trends Genet 1994;10:174-178
20 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;27:113-119   DOI   ScienceOn
21 Balzarini J, Bohman C, De Clercq E. Differential mechanism of cytostatic effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine, 9-(1,3-dihydroxy-2- propoxymethyl) guanine, and other antiherpetic drugs on tumor cells transfected by the thymidine kinase gene of herpes simplex virus type 1 or type 2. J Biol Chem 1993;268:6332-6337   PUBMED