Skip to main content Accessibility help
×
Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-28T03:33:26.212Z Has data issue: false hasContentIssue false

13 - Clinical Applications of Reporter Gene Technology

Published online by Cambridge University Press:  07 September 2010

Sanjiv Sam Gambhir
Affiliation:
Stanford University School of Medicine, California
Shahriar S. Yaghoubi
Affiliation:
Stanford University School of Medicine, California
Get access

Summary

INTRODUCTION

For more than a decade, molecular imaging (MI) has increasingly been used to successfully image gene expression in living animals, thus making significant contributions to the field of gene and cellular gene therapy. However, there has been slow progress in translating these technologies into clinical application, even though there is a real need to develop, test, and validate sensitive and reproducible noninvasive imaging methods that could be repeatedly and safely performed in patients undergoing gene therapy.

New molecular biology technologies now permit rapid determination of expression levels of hundreds of genes from minute tissue samples. These technologies combined with the complete sequencing of the human genome have allowed establishment of a molecular signature for many diseases. Nonetheless, gene expression patterns can change during the course of the pathology and in response to therapy. Such modification of gene expression patterns can alter drug sensitivity. Hence, molecular imaging can play a role in monitoring variation of gene expression during treatment.

Molecular imaging is emerging as a noninvasive technology for in vivo mapping of gene expression and provides promising tools for accelerated progress of molecular medicine (for a review see and references therein). Recently the importance of multimodality imaging has been recognized, allowing imaging of gene expression in intact cultured cells up to noninvasive whole-body imaging, both in animal models and in humans.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Hoffman, J. M., Gambhir, S. S. (2007). Molecular imaging: the vision and opportunity for radiology in the future. Radiology 244(1): 39–47.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
Massoud, T. F., Gambhir, S. S. (2007). Integrating noninvasive molecular imaging into molecular medicine: an evolving paradigm. Trends Mol Med 13(5): 183–191.Google Scholar
Penuelas, I., Boan, J., Marti-Climent, J. M., Sangro, B., Mazzolini, G., Prieto, J. et al. (2004). Positron emission tomography and gene therapy: basic concepts and experimental approaches for in vivo gene expression imaging. Mol Imaging Biol 6(4): 225–238.Google Scholar
Yaghoubi, S. S., Wu, L., Liang, Q., Toyokuni, T., Barrio, J. R., Namavari, M. et al. (2001). Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors. Gene Ther 8(14): 1072–1080.Google Scholar
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
Ray, P., Tsien, R., Gambhir, S. S. (2007). Construction and validation of improved triple fusion reporter gene vectors for molecular imaging of living subjects. Cancer Res 67(7): 3085–3093.Google Scholar
Deroose, C. M., De, A., Loening, A. M., Chow, P. L., Ray, P., Chatziioannou, A. F. et al. (2007). Multimodality imaging of tumor xenografts and metastases in mice with combined small-animal PET, small-animal CT, and bioluminescence imaging. J Nucl Med 48(2): 295–303.Google Scholar
Ponomarev, V., Doubrovin, M., Serganova, I., Vider, J., Shavrin, A., Beresten, T. et al. (2004). A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging. Eur J Nucl Med Mol Imaging 31(5): 740–751.Google Scholar
Ray, P., De, A., Min, J. J., Tsien, R. Y., Gambhir, S. S. (2004). Imaging tri-fusion multimodality reporter gene expression in living subjects. Cancer Res 64(4): 1323–1330.Google Scholar
Hielscher, A. H. (2005). Optical tomographic imaging of small animals. Curr Opin Biotechnol 16(1): 79–88.Google Scholar
Gibson, A. P., Hebden, J. C., Arridge, S. R. (2005). Recent advances in diffuse optical imaging. Phys Med Biol 50(4): R1–43.Google Scholar
Hawrysz, D. J., Sevick-Muraca, E. M. (2000). Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents. Neoplasia 2(5): 388–417.Google Scholar
Venisnik, K. M., Olafsen, T., Gambhir, S. S., Wu, A. M. (2007). Fusion of Gaussia luciferase to an engineered anti-carcinoembryonic antigen (CEA) antibody for in vivo optical imaging. Mol Imaging Biol 9(5): 267–277.Google Scholar
Labas, Y. A., Gurskaya, N. G., Yanushevich, Y. G., Fradkov, A. F., Lukyanov, K. A., Lukyanov, S. A. et al. (2002). Diversity and evolution of the green fluorescent protein family. Proc Natl Acad Sci U S A 99(7): 4256–4261.Google Scholar
Matz, M. V., Fradkov, A. F., Labas, Y. A., Savitsky, A. P., Zaraisky, A. G., Markelov, M. L. et al. (1999). Fluorescent proteins from nonbioluminescent Anthozoa species. Nat Biotechnol 17(10): 969–973.Google Scholar
Weissleder, R., Ntziachristos, V. (2003). Shedding light onto live molecular targets. Nat Med 9(1): 123–128.Google Scholar
Ntziachristos, V., Tung, C. H., Bremer, C., Weissleder, R. (2002). Fluorescence molecular tomography resolves protease activity in vivo. Nat Med 8(7): 757–760.Google Scholar
Funovics, M. A., Weissleder, R., Mahmood, U. (2004). Catheter-based in vivo imaging of enzyme activity and gene expression: feasibility study in mice. Radiology 231(3): 659–666.Google Scholar
Genove, G., DeMarco, U., Xu, H., Goins, W. F., Ahrens, E. T. (2005). A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 11(4): 450–454.Google Scholar
Cohen, B., Dafni, H., Meir, G., Harmelin, A., Neeman, M. (2005). Ferritin as an endogenous MRI reporter for noninvasive imaging of gene expression in C6 glioma tumors. Neoplasia 7(2): 109–117.Google Scholar
Gilad, A. A., McMahon, M. T., Walczak, P., Winnard, P. T., Raman, V., van Laarhoven, H. W. et al. (2007). Artificial reporter gene providing MRI contrast based on proton exchange. Nat Biotechnol 25(2): 217–219.Google Scholar
Gilad, A. A., Winnard, P. T., Zijl, P. C., Bulte, J. W. (2007). Developing MR reporter genes: promises and pitfalls. NMR Biomed 20(3): 275–290.Google Scholar
Beanlands, R., Roberts, R. (2007). Positron molecular imaging, an in vivo glimpse of the genome. J Mol Cell Cardiol 43(1): 11–14.Google Scholar
Rome, C., Couillaud, F., Moonen, C. T. (2007). Gene expression and gene therapy imaging. Eur Radiol 17(2): 305–319.Google Scholar
Penuelas, I., Haberkorn, U., Yaghoubi, S., Gambhir, S. S. (2005). Gene therapy imaging in patients for oncological applications. Eur J Nucl Med Mol Imaging 32(Suppl 2): S384–403.Google Scholar
Penuelas, I., Gambhir, S. S. (2005). Imaging studies for evaluating gene therapy in translational research. Drug Discovery Today: Technologies 2(4): 335–343.Google Scholar
Liang, Q., Satyamurthy, N., Barrio, J. R., Toyokuni, T., Phelps, M. P., Gambhir, S. S. et al. (2001). Noninvasive, quantitative imaging in living animals of a mutant dopamine D2 receptor reporter gene in which ligand binding is uncoupled from signal transduction. Gene Ther 8(19): 1490–1498.Google Scholar
MacLaren, D. C., Gambhir, S. S., Satyamurthy, N., Barrio, J. R., Sharfstein, S., Toyokuni, T. et al. (1999). Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals. Gene Ther 6(5): 785–791.Google Scholar
Zinn, K. R., Chaudhuri, T. R. (2002). The type 2 human somatostatin receptor as a platform for reporter gene imaging. Eur J Nucl Med Mol Imaging 29(3): 388–399.Google Scholar
Chung, J. K. (2002). Sodium iodide symporter: its role in nuclear medicine. J Nucl Med 43(9): 1188–1200.Google Scholar
Groot-Wassink, T., Aboagye, E. O., Glaser, M., Lemoine, N. R., Vassaux, G. (2002). Adenovirus biodistribution and noninvasive imaging of gene expression in vivo by positron emission tomography using human sodium/iodide symporter as reporter gene. Hum Gene Ther 13(14): 1723–1735.Google Scholar
Haberkorn, U., Henze, M., Altmann, A., Jiang, S., Morr, I., Mahmut, M. et al. (2001). Transfer of the human NaI symporter gene enhances iodide uptake in hepatoma cells. J Nucl Med 42(2): 317–325.Google Scholar
Anton, M., Wagner, B., Haubner, R., Bodenstein, C., Essien, B. E., Bonisch, H. et al. (2004). Use of the norepinephrine transporter as a reporter gene for non-invasive imaging of genetically modified cells. J Gene Med 6(1): 119–126.Google Scholar
Ponomarev, V., Doubrovin, M., Shavrin, A., Serganova, I., Beresten, T., Ageyeva, L. et al. (2007). A human-derived reporter gene for noninvasive imaging in humans: mitochondrial thymidine kinase type 2. J Nucl Med 48(5): 819–826.Google Scholar
Jacobs, A., Voges, J., Reszka, R., Lercher, M., Gossmann, A., Kracht, L. et al. (2001). Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 358(9283): 727–729.Google Scholar
Dempsey, M. F., Wyper, D., Owens, J., Pimlott, S., Papanastassiou, V., Patterson, J. et al. (2006). Assessment of 123I-FIAU imaging of herpes simplex viral gene expression in the treatment of glioma. Nucl Med Commun 27(8): 611–617.Google Scholar
Penuelas, I., Mazzolini, G., Boan, J. F., Sangro, B., Marti-Climent, J., Ruiz, M. et al. (2005). Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology 128(7): 1787–1795.Google Scholar
Jacobs, A. H., Rueger, M. A., Winkeler, A., Li, H., Vollmar, S., Waerzeggers, Y. et al. (2007). Imaging-guided gene therapy of experimental gliomas. Cancer Res 67(4): 1706–1715.Google Scholar
Weissleder, R. (2006). Molecular imaging in cancer. Science 312(5777): 1168–1171.Google Scholar
Phelps, M. E. (2004). Molecular Imaging and Its Biological Applications. 1st ed. New York: Springer-Verlag.
Weber, W. A. (2006). Positron emission tomography as an imaging biomarker. J Clin Oncol 24(20): 3282–3292.Google Scholar
Yaghoubi, S. S., Barrio, J. R., Namavari, M., Satyamurthy, N., Phelps, M. E., Herschman, H. R. et al. (2005). Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography. Cancer Gene Ther 12(3): 329–339.Google Scholar
Yaghoubi, S. S., Berger, F., Gambhir, S. S. (2007). Studying the biodistribution of positron emission tomography reporter probes in mice. Nat Protoc 2(7): 1752–1755.Google Scholar
Yaghoubi, S. S., Gambhir, S. S. (2006). PET imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk reporter gene expression in mice and humans using [18F]FHBG. Nat Protoc 1(6): 3069–3075.Google Scholar
Green, L. A., Nguyen, K., Berenji, B., Iyer, M., Bauer, E., Barrio, J. R. et al. (2004). A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET. J Nucl Med 45(9): 1560–1570.Google Scholar
Yaghoubi, S., Barrio, J. R., Dahlbom, M., Iyer, M., Namavari, M., Satyamurthy, N et al. (2001). Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. J Nucl Med 42(8): 1225–1234.Google Scholar
Yaghoubi, S. S., Couto, M. A., Chen, C. C., Polavaram, L., Cui, G., Sen, L. et al. (2006). Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression. J Nucl Med 47(4): 706–715.Google Scholar
Min, J. J., Iyer, M., Gambhir, S. S. (2003). 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 30(11): 1547–1560.Google Scholar
Tjuvajev, J. G., Doubrovin, M., Akhurst, T., Cai, S., Balatoni, J., Alauddin, M. M. et al. (2002). Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression. J Nucl Med 43(8): 1072–1083.Google Scholar
Kang, K. W., Min, J. J., Chen, X., Gambhir, S. S. (2005). 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 7(4): 296–303.Google Scholar
Buursma, A. R., Rutgers, V., Hospers, G. A., Mulder, N. H., Vaalburg, W., de Vries, E. F. (2006). 18F-FEAU as a radiotracer for herpes simplex virus thymidine kinase gene expression: in-vitro comparison with other PET tracers. Nucl Med Commun 27(1): 25–30.Google Scholar
Williams, D. A., Baum, C. (2003). Medicine. Gene therapy–new challenges ahead. Science 302(5644): 400–401.Google Scholar
Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M., Le Deist, F., Wulffraat, N., McIntyre, E. et al. (2003). A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 348(3): 255–256.Google Scholar
Thomas, C. E., Ehrhardt, A., Kay, M. A. (2003). Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet 4(5): 346–358.Google Scholar
Schellingerhout, D., Bogdanov, A., Marecos, E., Spear, M., Breakefield, X., Weissleder, R. (1998). Mapping the in vivo distribution of herpes simplex virions. Hum Gene Ther 9(11): 1543–1549.Google Scholar
Raty, J. K., Lesch, H. P., Wirth, T., Yla-Herttuala, S. (2008). Improving safety of gene therapy. Curr Drug Saf 3(1): 46–53.Google Scholar
Yaghoubi, S., Jensen, M. C., Satyamurthy, N., Budhiraja, S., Paik, D., Czernin, J. et al. (2008). Non-invasive detection of therapeutic cytolytic T cells with [18F]FHBG positron emission tomography in a glioma patient. Nature Clinical Practice Oncology 6(1): 53–58.Google Scholar
Adonai, N., Nguyen, K. N., Walsh, J., Iyer, M., Toyokuni, T., Phelps, M. E. et al. (2002). Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc Natl Acad Sci U S A 99(5): 3030–3035.Google Scholar
Tamura, M., Unno, K., Yonezawa, S., Hattori, K., Nakashima, E., Tsukada, H. et al. (2004). In vivo trafficking of endothelial progenitor cells their possible involvement in the tumor neovascularization. Life Sci 75(5): 575–584.Google Scholar
De, A., Lewis, X. Z., Gambhir, S. S. (2003). Noninvasive imaging of lentiviral-mediated reporter gene expression in living mice. Mol Ther 7(5 Pt 1): 681–691.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×