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6 - Cell-Specific Imaging of Reporter Gene Expression Using a Two-Step Transcriptional Amplification Strategy

Published online by Cambridge University Press:  07 September 2010

Sanjiv Sam Gambhir  and
Shahriar S. Yaghoubi
By
Marxa L. Figueiredo ,
Sanjiv Sam Gambhir ,
Michael Carey  and
Lily Wu
Sanjiv Sam Gambhir
Affiliation:
Stanford University School of Medicine, California
Shahriar S. Yaghoubi
Affiliation:
Stanford University School of Medicine, California
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Summary

INTRODUCTION

The monitoring of reporter gene expression allows measurement of the location(s), magnitude, and time variation of gene transcription in living animals and humans. Several imaging modalities can be employed for repetitive, noninvasive monitoring of reporter gene expression. The most common methods include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and optical imaging by bioluminescence (e.g., Firefly luciferase, Fluc, or luc) or fluorescence (e.g., green fluorescent protein, GFP). The strengths of each imaging modality are reviewed in Chapters 1–4. Noninvasive imaging has been applied extensively to monitor gene therapy, to detect cell migration and metastasis, and finally to monitor endogenous gene expression (by the use of transgenic mice expressing a reporter gene).

A common and successful means to target imaging of reporter gene expression to a particular tissue is to employ a transcriptional targeting strategy. Transcriptional targeting refers to the use of a cell-specific regulatory element (promoter or promoter/enhancer) to restrict gene expression to a particular tissue or cell type. A pitfall in using tissue- or tumor-specific promoters (TSPs) is that the relatively weak transcriptional activity of a cellular promoter could in principle greatly limit imaging sensitivity due to low levels of reporter gene expression in vivo. This contrasts with the potent but non-tissue–specific viral promoters like the simian virus 40 (SV40) early promoter or the cytomegalovirus (CMV) enhancer/promoter.

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Molecular Imaging with Reporter Genes , pp. 127 - 148
Publisher: Cambridge University Press
Print publication year: 2010

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References

Ray, P., Bauer, E., Iyer, M., Barrio, J. R., Satyamurthy, N., Phelps, M. E. et al. (2001). Monitoring gene therapy with reporter gene imaging. Semin Nucl Med 31(4): 312–320.Google Scholar
Wu, L., Johnson, M., Sato, M. (2003). Transcriptionally targeted gene therapy to detect and treat cancer. Trends Mol Med 9(10): 421–429.Google Scholar
Wu, L., Matherly, J., Smallwood, A., Adams, J. Y., Billick, E., Belldegrun, A. et al. (2001). Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors. Gene Ther 8(18): 1416–1426.Google Scholar
Lee, S. J., Kim, H. S., Yu, R., Lee, K., Gardner, T. A., Jung, C. et al. (2002). Novel prostate-specific promoter derived from PSA and PSMA enhancers. Mol Ther 6(3): 415–421.Google Scholar
Sadowski, I., Ma, J., Triezenberg, S., Ptashne, M. (1988). GAL4-VP16 is an unusually potent transcriptional activator. Nature 335(6190): 563–564.Google Scholar
Segawa, T., Takebayashi, H., Kakehi, Y., Yoshida, O., Narumiya, S., Kakizuka, A. (1998). Prostate-specific amplification of expanded polyglutamine expression: a novel approach for cancer gene therapy. Cancer Res 58(11): 2282–2287.Google Scholar
Figueiredo, M. L., Sato, M., Johnson, M., Wu, L. (2006). Specific targeting of gene therapy to prostate cancer using a two-step transcriptional amplification system. Future Oncol 2(3): 391–406.Google Scholar
Aumuller, G., Seitz, J., Lilja, H., Abrahamsson, P. A., der Kammer, H., Scheit, K.H. (1990). Species- and organ-specificity of secretory proteins derived from human prostate and seminal vesicles. Prostate 17(1): 31–40.Google Scholar
Zhang, L., Adams, J. Y., Billick, E., Ilagan, R., Iyer, M., Le, K. et al. (2002). Molecular engineering of a two-step transcription amplification (TSTA) system for transgene delivery in prostate cancer. Mol Ther 5(3): 223–232.Google Scholar
Cleutjens, K. B., Korput, H. A., Ehren-van Eekelen, C. C., Sikes, R. A., Fasciana, C., Chung, L. W. et al. (1997). A 6-kb promoter fragment mimics in transgenic mice the prostate-specific and androgen-regulated expression of the endogenous prostate-specific antigen gene in humans. Mol Endocrinol 11(9): 1256–1265.Google Scholar
Cleutjens, K. B., Korput, H. A., Eekelen, C. C., Rooij, H. C., Faber, P. W., Trapman, J. (1997). An androgen response element in a far upstream enhancer region is essential for high, androgen-regulated activity of the prostate-specific antigen promoter. Mol Endocrinol 11(2): 148–161.Google Scholar
Schaffner, D. L., Barrios, R., Shaker, M. R., Rajagopalan, S., Huang, S. L., Tindall, D. J. et al. (1995). Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms. Lab Invest 72(3): 283–290.Google Scholar
Yeung, F., Li, X., Ellett, J., Trapman, J., Kao, C., Chung, L.W. (2000). Regions of prostate-specific antigen (PSA) promoter confer androgen-independent expression of PSA in prostate cancer cells. J Biol Chem 275(52): 40846–40855.Google Scholar
Titus, M. A., Schell, M. J., Lih, F. B., Tomer, K. B., Mohler, J. L. (2005). Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin Cancer Res 11(13): 4653–4657.Google Scholar
Zhang, L., Johnson, M., Le, K. H., Sato, M., Ilagan, R., Iyer, M. et al. (2003). Interrogating androgen receptor function in recurrent prostate cancer. Cancer Res 63(15): 4552–4560.Google Scholar
Sato, M., Johnson, M., Zhang, L., Gambhir, M.Carey, and Wu, L. (2005). Functionality of androgen receptor-based gene expression imaging in hormone refractory prostate cancer. Clin Cancer Res 11(10): 3743–3749.Google Scholar
Pang, S., Dannull, J., Kaboo, R., Xie, Y., Tso, C. L., Michel, K. et al. (1997). Identification of a positive regulatory element responsible for tissue-specific expression of prostate-specific antigen. Cancer Res 57(3): 495–499.Google Scholar
Adams, J. Y., Johnson, M., Sato, M., Berger, F., Gambhir, S. S., Carey, M. et al. (2002). Visualization of advanced human prostate cancer lesions in living mice by a targeted gene transfer vector and optical imaging. Nat Med 8(8): 891–897.Google Scholar
Iyer, M., Wu, L., Carey, M., Wang, Y., Smallwood, A., Gambhir, S. S. (2001). Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters. Proc Natl Acad Sci U S A 98(25): 14595–14600.Google Scholar
Qiao, J., Doubrovin, M., Sauter, B. V., Huang, Y., Guo, Z. S., Balatoni, J. et al. (2002). Tumor-specific transcriptional targeting of suicide gene therapy. Gene Ther 9(3): 168–175.Google Scholar
Sato, M., Johnson, M., Zhang, L., Zhang, B., Le, K., Gambhir, S. S. et al. (2003). Optimization of adenoviral vectors to direct highly amplified prostate-specific expression for imaging and gene therapy. Mol Ther 8(5): 726–737.Google Scholar
Johnson, M., Sato, M., Burton, J., Gambhir, S. S., Carey, M., Wu, L. (2005). Micro-PET/CT monitoring of herpes thymidine kinase suicide gene therapy in a prostate cancer xenograft: The advantage of a cell-specific transcriptional targeting approach. Mol Imaging 4(4): 463–472.Google Scholar
Ilagan, R., Zhang, L. J., Pottratz, J., Le, K., Salas, S., Iyer, M. et al. (2005). Imaging androgen receptor function during flutamide treatment in the LAPC9 xenograft model. Mol Cancer Ther 4(11): 1662–1669.Google Scholar
Johnson, M., Huyn, S., Burton, J., Sato, M., Wu, L. (2006). Differential biodistribution of adenoviral vector in vivo as monitored by bioluminescence imaging and quantitative polymerase chain reaction. Hum Gene Ther 17(12): 1262–1269.Google Scholar
Sato, M., Figueiredo, M. L., Burton, J. B., Johnson, M., Chen, M., Powell, R. et al. (2008). Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging. Gene Ther 15(8): 583–593.Google Scholar
Ray, S., Paulmurugan, R., Hildebrandt, I., Iyer, M., Wu, L., Carey, M. et al. (2004). Novel bidirectional vector strategy for amplification of therapeutic and reporter gene expression. Hum Gene Ther 15(7): 681–690.Google Scholar
Ray, S., Paulmurugan, R., Patel, M. R., Ahn, B. C., Wu, L., Carey, M. et al. (2008). Noninvasive imaging of therapeutic gene expression using a bidirectional transcriptional amplification strategy. Mol Ther.CrossRef
Iyer, M., Salazar, F. B., Lewis, X., Zhang, L., Carey, M., Wu, L. et al. (2004). Noninvasive imaging of enhanced prostate-specific gene expression using a two-step transcriptional amplification-based lentivirus vector. Mol Ther 10(3): 545–552.Google Scholar
Iyer, M., Salazar, F. B., Wu, L., Carey, M., Gambhir, S. S. (2006). Bioluminescence imaging of systemic tumor targeting using a prostate-specific lentiviral vector. Hum Gene Ther 17(1): 125–132.Google Scholar
Wang, Y., Iyer, M., Annala, A., Wu, L., Carey, M., Gambhir, S. S. (2006). Noninvasive indirect imaging of vascular endothelial growth factor gene expression using bioluminescence imaging in living transgenic mice. Physiol Genomics 24(2): 173–180.Google Scholar
Ilagan, R., Pottratz, J., Le, K., Zhang, L., Wong, S. G., Ayala, R. et al. (2006). Imaging mitogen-activated protein kinase function in xenograft models of prostate cancer. Cancer Res 66(22): 10778–10785.Google Scholar
Massoud, T. F., Gambhir, S. S. (2003). Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17(5): 545–580.Google Scholar
Iyer, M., Sato, M., Johnson, M., Gambhir, S. S., Wu, L. (2005). Applications of molecular imaging in cancer gene therapy. Curr Gene Ther 5(6): 607–618.Google Scholar
Brakenhielm, E., Burton, J. B., Johnson, M., Chavarria, N., Morizono, K., Chen, I. et al. (2007). Modulating metastasis by a lymphangiogenic switch in prostate cancer. Int J Cancer 121(10): 2153–2161.Google Scholar
Burton, J. B., Johnson, M., Sato, M., Koh, S. B., Mulholland, D. J., Stout, D. et al. (2008). Adenovirus-mediated gene expression imaging to directly detect sentinel lymph node metastasis of prostate cancer. Nat Med 14(8): 882–888.Google Scholar
Block, A., Milasinovic, D., Mueller, J., Schaefer, P., Schaefer, H., Greten, H. (2002). Amplified Muc1-specific gene expression in colon cancer cells utilizing a binary system in adenoviral vectors. Anticancer Res 22(6A): 3285–3292.Google Scholar
Xie, X., Xia, W., Li, Z., Kuo, H. P., Liu, Y., Ding, Q. et al. (2007). Targeted expression of BikDD eradicates pancreatic tumors in noninvasive imaging models. Cancer Cell 12(1): 52–65.Google Scholar
Richards, C. A., Austin, E. A., Huber, B. E. (1995). Transcriptional regulatory sequences of carcinoembryonic antigen: identification and use with cytosine deaminase for tumor-specific gene therapy. Hum Gene Ther 6(7): 881–893.Google Scholar
Siders, W. M., Halloran, P. J., Fenton, R. G. (1998). Melanoma-specific cytotoxicity induced by a tyrosinase promoter-enhancer/herpes simplex virus thymidine kinase adenovirus. Cancer Gene Ther 5(5): 281–291.Google Scholar
Koch, P. E., Guo, Z. S., Kagawa, S., Gu, J., Roth, J. A., Fang, B. (2001). Augmenting transgene expression from carcinoembryonic antigen (CEA) promoter via a GAL4 gene regulatory system. Mol Ther 3(3): 278–283.Google Scholar
Zhang, D., Sutanto, E. N., Rakoczy, P. E. (2004). Concurrent enhancement of transcriptional activity and specificity of a retinal pigment epithelial cell-preferential promoter. Mol Vis 10: 208–214.Google Scholar
Dzojic, H., Cheng, W. S., Essand, M. (2007). Two-step amplification of the human PPT sequence provides specific gene expression in an immunocompetent murine prostate cancer model. Cancer Gene Ther 14(3): 233–240.Google Scholar
Woraratanadharm, J., Rubinchik, S., Yu, H., Fan, F., Morrow, S. M., Dong, J. Y. (2004). Highly specific transgene expression mediated by a complex adenovirus vector incorporating a prostate-specific amplification feedback loop. Gene Ther 11(18): 1399–1407.Google Scholar
Sato, Y., Tanaka, K., Lee, G., Kanegae, Y., Sakai, Y., Kaneko, S. et al. (1998). Enhanced and specific gene expression via tissue-specific production of Cre recombinase using adenovirus vector. Biochem Biophys Res Commun 244(2): 455–462.Google Scholar
Yoshimura, I., Ikegami, S., Suzuki, S., Tadakuma, T., Hayakawa, M. (2002). Adenovirus mediated prostate specific enzyme prodrug gene therapy using prostate specific antigen promoter enhanced by the Cre-loxP system. J Urol 168(6): 2659–2664.Google Scholar
Ikegami, S., Tadakuma, T., Suzuki, S., Yoshimura, I., Asano, T., Hayakawa, M. (2002). Development of gene therapy using prostate-specific membrane antigen promoter/enhancer with Cre Recombinase/LoxP system for prostate cancer cells under androgen ablation condition. Jpn J Cancer Res 93(10): 1154–1163.Google Scholar
Ikegami, S., Tadakuma, T., Ono, T., Suzuki, S., Yoshimura, I., Asano, T. et al. (2004). Treatment efficiency of a suicide gene therapy using prostate-specific membrane antigen promoter/enhancer in a castrated mouse model of prostate cancer. Cancer Sci 95(4): 367–370.Google Scholar
Kaczmarczyk, S. J., Green, J. E. (2003). Induction of cre recombinase activity using modified androgen receptor ligand binding domains: a sensitive assay for ligand-receptor interactions. Nucleic Acids Res 31(15): e86.Google Scholar
Sundaresan, G., Paulmurugan, R., Berger, F., Stiles, B., Nagayama, Y., Wu, H. et al. (2004). MicroPET imaging of Cre-loxP-mediated conditional activation of a herpes simplex virus type 1 thymidine kinase reporter gene. Gene Ther 11(7): 609–618.Google Scholar
Koster, R. W., Fraser, S. E. (2001). Tracing transgene expression in living zebrafish embryos. Dev Biol 233(2): 329–346.Google Scholar
Loonstra, A., Vooijs, M., Beverloo, H. B., Allak, B. A., van Drunen, E., Kanaar, R. et al. (2001). Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells. Proc Natl Acad Sci U S A 98(16): 9209–9214.Google Scholar
Wang, H. U., Chen, Z. F., Anderson, D. J. (1998). Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93(5): 741–753.Google Scholar
Braselmann, S., Graninger, P., Busslinger, M. (1993). A selective transcriptional induction system for mammalian cells based on Gal4-estrogen receptor fusion proteins. Proc Natl Acad Sci U S A 90(5): 1657–1661.Google Scholar
Rivera, V. M., Clackson, T., Natesan, S., Pollock, R., Amara, J. F., Keenan, T. et al. (1996). A humanized system for pharmacologic control of gene expression. Nat Med 2(9): 1028–1032.Google Scholar
Pollock, R., Clackson, T. (2002). Dimerizer-regulated gene expression. Curr Opin Biotechnol 13(5): 459–467.Google Scholar
Nguyen, M., Huan-Tu, G., Gonzalez-Edick, M., Rivera, V. M., Clackson, T., Jooss, K.U. et al. (2007). Rapamycin- regulated control of antiangiogenic tumor therapy following rAAV-mediated gene transfer. Mol Ther 15(5): 912–920.Google Scholar
Stevenson, M., Hale, A. B., Hale, S. J., Green, N. K., Black, G., Fisher, K. D. et al. (2007). Incorporation of a laminin-derived peptide (SIKVAV) on polymer-modified adenovirus permits tumor-specific targeting via alpha6-integrins. Cancer Gene Ther 14(4): 335–345.Google Scholar
Bonsted, A., Engesaeter, B. O., Hogset, A., Maelandsmo, G. M., Prasmickaite, L., D'Oliveira, C. et al. (2006). Photochemically enhanced transduction of polymer-complexed adenovirus targeted to the epidermal growth factor receptor. J Gene Med 8(3): 286–297.Google Scholar
Kraaij, R., Rijswijk, A. L., Oomen, M. H., Haisma, H. J., Bangma, C. H. (2005). Prostate specific membrane antigen (PSMA) is a tissue-specific target for adenoviral transduction of prostate cancer in vitro. Prostate 62(3): 253–259.Google Scholar

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