Volume 30 Issue 5
Oct.  2006
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The development of herpes simplex virus thyInidine kinase suicide gene imaging

  • Suicide gene treatment of tumor catches more and more attention in recent years. Cells transferred with suicide gene from virus or bacteria will express specific enzymes and transform innocuous prodrugs into highly toxic chemotherapeutic drugs. As a result, the cells will be killed. Radionuclide labeled probe can display the biologic characteristics of suicide gene in vivo. This article reviews the development of HSV-tk gene imaging.
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  • [1] Caroline JS,Ion ND.Prodrug-activating systems in suicide gene therapy.J Clin Invest,2000,105(9):1161-1167.
    [2] Burrows FJ,Gore M,Smiley WR,et al.Purified herpes simplex virus thymidine kinase retroviral particles:Ⅲ.Characterization of bystander killing mechanisms in transfected tumor cells.Cancer Gene Ther,2002,9(1):87-95.
    [3] Dilber MS,Gahrton G.Suicide gene therapy:possible applications in haematopoietic disorders.J Intern Med,2001,249(4):359-367.
    [4] Hasenburg A,Tong XW,Rojas-Martinez A,et al.Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer.Cancer Gene Ther,2000,7(6):839-844.
    [5] Ayala G,Wheeler TM,Shalev M,et al.Cytopathic effect of in situ gene therapy in prostate cancer.Hum Pathol,2000,31(7):866-870.
    [6] Shalev M,Kadmon D,Teh BS,et al.Suicide gene therapy toxicity after multiple and repeat injections in patients with localized prostate cancer.J Urol,2000,163(6):1747-1750.
    [7] Morris JC,Ramsey WJ,Wildner O,et al.A phase I study of intralesional administration of an adenovirus vector expressing the HSV-1 thymidine kinase gene (AdV.RSV-TK) in combination with escalating doses of ganciclovir in patients with cutaneous metastatic malignant melanoma.Hum Gene Ther,2000,11(3):487-503.
    [8] Buursma AR,van Dillen I J,van Waarde A,et al.Monitoring HSVtk suicide gene therapy:the role of[(18) F] FHPG membrane transport.Br J Cancer,2004,91(12):2079-2085.
    [9] Alauddin MM,Shahinian A,Gordon EM,et al.Preclinical evaluation of the penciclovir analog 9-(4-[18F] fluoro-3-hydroxymethylbutyl) guanine for in vivo measurement of suicide gene expression with PET.J Nucl Med,2001,42(11):1682-1690.
    [10] Iyer M,Barrio JR,Namavari M,et al.8-[18F] fluoropenciclovir:an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET.J Nucl Med,2001,42(8):96-105.
    [11] Alauddin MM,Shahinian A,Gordon EM,et al.Evaluation of 2'-deoxy-2'-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU) as a potential gene imaging agent for HSV-tk expression in vivo.Mol Imaging,2002,1(2):74-81.
    [12] Tjuvajev JG,Doubrovin M,Akhurst T,et al.Direct comparison of HSV-tk PET imaging probes:FIAU,FHPG,FHBG.J Nucl Med,2002,43(8):1072-1083.
    [13] Alauddin MM,Shahinian A,Park R,et al.Synthesis and evaluation of 2'-deoxy-2'-18F-fluoro-5-fluoro-1-beta-D-arabinofuranosyluracil as a potential PET imaging agent for suicide gene expression.J Nucl Med,2004,45(12):2063-2069.
    [14] Choi SR,Zhuang ZP,Chacko AM,et al.SPECT imaging of herpes simplex virus type1 thymidine kinase gene expression by[(123)I] FIAU.Acad Radiol,2005,12(7):798-805.
    [15] Frank O,Rudolph C,Heberlein C,et al.Tumor cells escape suicide gene therapy by genetic and epigenetic instability.Blood,2004,104(12):3543-3549.
    [16] Curiel DT.Strategies to adapt adenoviral vectors for targeted delivery.Ann NY Acad Sci,1999,886:158-171.
    [17] Shillitoe EJ,Noonan S.Strength and specificity of different gene promoters in oral cancer cells.Oral Oncol,2000,36(2):214-220.
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The development of herpes simplex virus thyInidine kinase suicide gene imaging

    Corresponding author: ZHAO Jin-hua, zjh1963@gmail.com
  • Department of Nuclear Medicine, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China

Abstract: Suicide gene treatment of tumor catches more and more attention in recent years. Cells transferred with suicide gene from virus or bacteria will express specific enzymes and transform innocuous prodrugs into highly toxic chemotherapeutic drugs. As a result, the cells will be killed. Radionuclide labeled probe can display the biologic characteristics of suicide gene in vivo. This article reviews the development of HSV-tk gene imaging.

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