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Central European Journal of Biology

, Volume 1, Issue 1, pp 88–123 | Cite as

Non-invasive molecular imaging and reporter genes

  • Inna Serganova
  • Ekaterina Moroz
  • Maxim Moroz
  • Nagavarakishore Pillarsetty
  • Ronald Blasberg
Research Article

Abstract

Molecular-genetic imaging in living organisms has become a new field with the exceptional growth over the past 5 years. Modern imaging is based on three technologies: nuclear, magnetic resonance and optical imaging. Most current molecular-genetic imaging strategies are “indirect,” coupling a “reporter gene” with a complimentary “reporter probe.” The reporter transgene usually encodes for an enzyme, receptor or transporter that selectively interacts with a radiolabeled probe and results in accumulation of radioactivity in the transduced cell. In addition, reporter systems based on the expression of fluorescence or bioluminescence proteins are becoming more widely applied in small animal imaging. This review begins with a description of Positron Emission Tomography (PET)-based imaging genes and their complimentary radiolabeled probes that we think will be the first to enter clinical trials. Then we describe other imaging genes, mostly for optical imaging, which have been developed by investigators working with a variety of disease models in mice. Such optical reporters are unlikely to enter the clinic, at least not in the near-term. Reporter gene constructs can be driven by constitutive promoter elements and used to monitor gene therapy vectors and the efficacy of gene targeting and transduction, as well as to monitor adoptive cell-based therapies. Inducible promoters can be used as “sensors” to monitor endogenous cell processes, including specific intracellular molecular-genetic events and the activity of signaling pathways, by regulating the magnitude of reporter gene expression.

Keywords

Reporter (imaging) genes nuclear reporters fluorescence reporters optical reporters viral delivery PET — positron emission tomography in vivo imaging 

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References

  1. [1]
    S. Forss-Petter, P.E. Danielson, S. Catsicas, E. Battenberg, J. Price, M. Nerenberg and J.G. Sutcliffe: “Transgenic mice expressing beta-galactosidase in mature neurons under neuron-specific enolase promoter control”, Neuron, Vol. 5, (1990), pp. 187–197.PubMedCrossRefGoogle Scholar
  2. [2]
    P.A. Overbeek, A.B. Chepelinsky, J.S. Khillan, J. Piatigorsky and H. Westphal: “Lens-specific expression and developmental regulation of the bacterial chloramphenicol acetyltransferase gene driven by the murine alpha A-crystallin promoter in transgenic mice”, Proc. Natl. Acad. Sci. U.S.A., Vol. 82, (1985), pp. 7815–7819.PubMedCrossRefGoogle Scholar
  3. [3]
    R. Blasberg: “Imaging gene expression and endogenous molecular processes: molecular imaging”, J. Cereb. Blood Flow Metab., Vol. 22, (2002), pp. 1157–1164.PubMedCrossRefGoogle Scholar
  4. [4]
    S.S. Gambhir: “Molecular imaging of cancer with positron emission tomography”, Nat. Rev. Cancer, Vol. 2, (2002), pp. 683–693.PubMedCrossRefGoogle Scholar
  5. [5]
    V. Ntziachristos, C.H. Tung, C. Bremer and R. Weissleder: “Fluorescence molecular tomography resolves protease activity in vivo”, Nat. Med., Vol. 8, (2002), pp. 757–760.PubMedCrossRefGoogle Scholar
  6. [6]
    V. Ntziachristos, J. Ripoll, L.V. Wang and R. Weissleder: “Looking and listening to light: the evolution of whole-body photonic imaging”, Nat. Biotechnol., Vol. 23, (2005), pp. 313–320.PubMedCrossRefGoogle Scholar
  7. [7]
    G. Genove, U. DeMarco, H. Xu, W.F. Goins and E.T. Ahrens: “A new transgene reporter for in vivo magnetic resonance imaging”, Nat. Med., Vol. 11, (2005), pp. 450–454.PubMedCrossRefGoogle Scholar
  8. [8]
    R. Weissleder and V. Ntziachristos: “Shedding light onto live molecular targets”, Nat. Med., Vol. 9, (2003), pp. 123–128.PubMedCrossRefGoogle Scholar
  9. [9]
    B.N. Chievitz and O.G. de Hevesy: “Radioactive indicators in the study of phosphorous metabolism in rats”, Nature, Vol. 1935, (1935), p. 754.Google Scholar
  10. [10]
    R.G. Blasberg and J.G. Tjuvajev: “Molecular-genetic imaging: current and future perspectives”, J. Clin. Invest., Vol. 111, (2003), pp. 1620–1629.PubMedCrossRefGoogle Scholar
  11. [11]
    M. Doubrovin, I. Serganova, P. Mayer-Kuckuk, V. Ponomarev and R.G. Blasberg: “Multimodality in vivo molecular-genetic imaging”, Bioconjug. Chem., Vol. 15, (2004), pp. 1376–1388.PubMedCrossRefGoogle Scholar
  12. [12]
    J.G. Tjuvajev, A. Joshi, J. Callegari, L. Lindsley, R. Joshi, J. Balatoni, R. Finn, S.M. Larson, M. Sadelain and R.G. Blasberg: “A general approach to the non-invasive imaging of transgenes using cis-linked herpes simplex virus thymidine kinase”, Neoplasia, Vol. 1, (1999), pp. 315–320.PubMedCrossRefGoogle Scholar
  13. [13]
    I. Serganova and R. Blasberg: “Reporter gene imaging: potential impact on therapy”, Nucl. Med. Biol. Vol. 32, (2005), pp. 763–780.PubMedCrossRefGoogle Scholar
  14. [14]
    C.L. Brumley and J.A. Kuhn: “Radiolabeled monoclonal antibodies”, AORN J., Vol. 62, (1995), pp. 343–350, 353-345; quiz 356-348, 361-342.PubMedGoogle Scholar
  15. [15]
    Z. Tu, C.S. Dence, D.E. Ponde, L. Jones, K.T. Wheeler, M.J. Welch and R.H. Mach: “Carbon-11 labeled sigma2 receptor ligands for imaging breast cancer”, Nucl. Med. Biol., Vol. 32, (2005), pp. 423–430.PubMedCrossRefGoogle Scholar
  16. [16]
    X. Chen, E. Sievers, Y. Hou, R. Park, M. Tohme, R. Bart, R. Bremner, J.R. Bading and P.S. Conti: “Integrin alpha v beta 3-targeted imaging of lung cancer”, Neoplasia, Vol. 7, (2005), pp. 271–279.PubMedGoogle Scholar
  17. [17]
    H.R. Herschman: “Noninvasive imaging of reporter gene expression in living subjects”, Adv. Cancer Res., Vol. 92, (2004), pp. 29–80.PubMedCrossRefGoogle Scholar
  18. [18]
    R.G. Blasberg: “Receptor binding radiotracers: personal history of the past 20 years”, Nucl. Med. Biol., Vol. 28, (2001), pp. 573–583.PubMedCrossRefGoogle Scholar
  19. [19]
    M.R. Acker and S.C. Burrell: “Utility of 18F-FDG PET in evaluating cancers of lung”, J. Nucl. Med. Technol., Vol. 33, (2005), pp. 69–74; quiz 75-67.PubMedGoogle Scholar
  20. [20]
    A. Quon and S.S. Gambhir: “FDG-PET and beyond: molecular breast cancer imaging”, J. Clin. Oncol., Vol. 23, (2005), pp. 1664–1673.PubMedCrossRefGoogle Scholar
  21. [21]
    C.H. Contag, S.D. Spilman, P.R. Contag, M. Oshiro, B. Eames, P. Dennery, D.K. Stevenson and D.A. Benaron: “Visualizing gene expression in living mammals using a bioluminescent reporter”, Photochem. Photobiol., Vol. 66, (1997), pp. 523–531.PubMedGoogle Scholar
  22. [22]
    P.R. Contag, I.N. Olomu, D.K. Stevenson and C.H. Contag: “Bioluminescent indicators in living mammals”, Nat. Med., Vol. 4, (1998), pp. 245–247.PubMedCrossRefGoogle Scholar
  23. [23]
    A. Rehemtulla, L.D. Stegman, S.J. Cardozo, S. Gupta, D.E. Hall, C.H. Contag and B.D. Ross: “Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging”, Neoplasia, Vol. 2, (2000), pp. 491–495.PubMedCrossRefGoogle Scholar
  24. [24]
    J.G. Tjuvajev, G. Stockhammer, R. Desai, H. Uehara, K. Watanabe, B. Gansbacher and R.G. Blasberg: “Imaging the expression of transfected genes in vivo”, Cancer Res., Vol. 55, (1995), pp. 6126–6132.PubMedGoogle Scholar
  25. [25]
    J.G. Tjuvajev, R. Finn, K. Watanabe, R. Joshi, T. Oku, J. Kennedy, B. Beattie, J. Koutcher, S. Larson and R.G. Blasberg: “Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy”, Cancer Res., Vol. 56, (1996), pp. 4087–4095.PubMedGoogle Scholar
  26. [26]
    J.G. Tjuvajev, N. Avril, T. Oku, T. Sasajima, T. Miyagawa, R. Joshi, M. Safer, B. Beattie, G. DiResta, F. Daghighian, F. Augensen, J. Koutcher, J. Zweit, J. Humm, S.M. Larson, R. Finn and R. Blasberg: “Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography”, Cancer Res., Vol. 58, (1998), pp. 4333–4341.PubMedGoogle Scholar
  27. [27]
    S.S. Gambhir, J.R. Barrio, M.E. Phelps, M. Iyer, M. Namavari, N. Satyamurthy, L. Wu, L.A. Green, E. Bauer, D.C. MacLaren, K. Nguyen, A.J. Berk, S.R. Cherry and H.R. Herschman: “Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography”, Proc. Natl. Acad. Sci. U.S.A., Vol. 96, (1999), pp. 2333–2338.PubMedCrossRefGoogle Scholar
  28. [28]
    S.S. Gambhir, J.R. Barrio, L. Wu, M. Iyer, M. Namavari, N. Satyamurthy, E. Bauer, C. Parrish, D.C. MacLaren, A.R. Borghei, L.A. Green, S. Sharfstein, A.J. Berk, S.R. Cherry, M.E. Phelps and H.R. Herschman: “Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir”, J. Nucl. Med., Vol. 39, (1998), pp. 2003–2011.PubMedGoogle Scholar
  29. [29]
    R. Weissleder, M. Simonova, A. Bogdanova, S. Bredow, W.S. Enochs and A. Bogdanov Jr.: “MR imaging and scintigraphy of gene expression through melanin induction”, Radiology, Vol. 204, (1997), pp. 425–429.PubMedGoogle Scholar
  30. [30]
    A.Y. Louie, M.M. Huber, E.T. Ahrens, U. Rothbacher, R. Moats, R.E. Jacobs, S.E. Fraser and T.J. Meade: “In vivo visualization of gene expression using magnetic resonance imaging”, Nat. Biotechnol., Vol. 18, (2000), pp. 321–325.PubMedCrossRefGoogle Scholar
  31. [31]
    K.R. Zinn and T.R. Chaudhuri: “The type 2 human somatostatin receptor as a platform for reporter gene imaging”, Eur. J. Nucl. Med. Mol. Imaging., Vol. 29, (2002), pp. 388–399.PubMedCrossRefGoogle Scholar
  32. [32]
    A. Boland, M. Ricard, P. Opolon, J.M. Bidart, P. Yeh, S. Filetti, M. Schlumberger and M. Perricaudet: “Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy”, Cancer Research, Vol. 60, (2000), pp. 3484–3492.PubMedGoogle Scholar
  33. [33]
    J.C. March, G. Rao and W.E. Bentley: “Biotechnological applications of green fluorescent protein”, Appl. Microbiol. Biotechnol., Vol. 62, (2003), pp. 303–315.PubMedCrossRefGoogle Scholar
  34. [34]
    R.M. Hoffman: “Advantages of multi-color fluorescent proteins for whole-body and in vivo cellular imaging”, J. Biomed. Opt.,Vol. 10, (2005), p. 41202.PubMedCrossRefGoogle Scholar
  35. [35]
    A.D. Van den Abbeele and R.D. Badawi: “Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs)”, Eur. J. Cancer, Vol. 38(Suppl 5), (2002), pp. S60–S65.PubMedGoogle Scholar
  36. [36]
    J.A. Fyfe, P.M. Keller, P.A. Furman, R.L. Miller and G.B. Elion: “Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine”, J. Biol. Chem. Vol. 253, (1978), pp. 8721–8727.PubMedGoogle Scholar
  37. [37]
    D. Klatzmann, P. Cherin, G. Bensimon, O. Boyer, A. Coutellier, F. Charlotte, C. Boccaccio, J.L. Salzmann and S. Herson: “A phase I/II dose-escalation study of herpes simplex virus type 1 thymidine kinase “suicide” gene therapy for metastatic melanoma. Study Group on Gene Therapy of Metastatic Melanoma”, Hum. Gene Ther., Vol. 9, (1998), pp. 2585–2594.PubMedCrossRefGoogle Scholar
  38. [38]
    Z. Ram, K.W. Culver, E.M. Oshiro, J.J. Viola, H.L. De Vroom, E. Otto, Z. Long, Y. Chiang, G.J. McGarrity, L.M. Muul, D. Katz, R.M. Blaese and E.H. Oldfield: “Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells”, Nat. Med., Vol. 3, (1997), pp. 1354–1361.PubMedCrossRefGoogle Scholar
  39. [39]
    Y. Saito, R.W. Price, D.A. Rottenberg, J.J. Fox, T.L. Su, K.A. Watanabe and F.S. Philips: “Quantitative autoradiographic mapping of herpes simplex virus encephalitis with a radiolabeled antiviral drug”, Science, Vol. 217, (1982), pp. 1151–1153.PubMedGoogle Scholar
  40. [40]
    A. Jacobs, J. Voges, R. Reszka, M. Lercher, A. Gossmann, L. Kracht, C. Kaestle, R. Wagner, K. Wienhard and W.D. Heiss: “Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas”, Lancet, Vol. 358, (2001), pp. 727–729.PubMedCrossRefGoogle Scholar
  41. [41]
    M.M. Alauddin and P.S. Conti: “Synthesis and preliminary evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG): a new potential imaging agent for viral infection and gene therapy using PET”, Nucl. Med. Biol., Vol. 25, (1998), pp. 175–180.PubMedCrossRefGoogle Scholar
  42. [42]
    M. Iyer, J.R. Barrio, M. Namavari, E. Bauer, N. Satyamurthy, K. Nguyen, T. Toyokuni, M.E. Phelps, H.R. Herschman and S.S. Gambhir: “8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET”, J. Nucl. Med., Vol. 42, (2001), pp. 96–105.PubMedGoogle Scholar
  43. [43]
    S.S. Gambhir, E. Bauer, M.E. Black, Q. Liang, M.S. Kokoris, J.R. Barrio, M. Iyer, M. Namavari, M.E. Phelps and H.R. Herschman: “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. U.S.A., Vol. 97, (2000), pp. 2785–2790.PubMedCrossRefGoogle Scholar
  44. [44]
    S.S. Yaghoubi, J.R. Barrio, M. Namavari, N. Satyamurthy, M.E. Phelps, H.R. Herschman and S.S. Gambhir: “Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography”, Cancer Gene Ther., Vol. 12, (2005), pp. 329–339.PubMedCrossRefGoogle Scholar
  45. [45]
    I. Penuelas, G. Mazzolini, J.F. Boan, B. Sangro, J. Marti-Climent, M. Ruiz, J. Ruiz, N. Satyamurthy, C. Qian, J.R. Barrio, M.E. Phelps, J.A. Richter, S.S. Gambhir and J. Prieto: “Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients”, Gastroenterology, Vol. 128, (2005), pp. 1787–1795.PubMedCrossRefGoogle Scholar
  46. [46]
    I. Penuelas, U. Haberkorn, S. Yaghoubi and S.S. Gambhir: “Gene therapy imaging in patients for oncological applications”, Eur. J. Nucl. Med. Mol. Imaging Suppl. 2, (2005), pp. s384–403.CrossRefGoogle Scholar
  47. [47]
    M. Doubrovin, V. Ponomarev, T. Beresten, J. Balatoni, W. Bornmann, R. Finn, J. Humm, S. Larson, M. Sadelain, R. Blasberg and J. Gelovani Tjuvajev: “Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo”, Proc. Natl. Acad. Sci. U.S.A., Vol. 98, (2001), pp. 9300–9305.PubMedCrossRefGoogle Scholar
  48. [48]
    I. Serganova, M. Doubrovin, J. Vider, V. Ponomarev, S. Soghomonyan, T. Beresten, L. Ageyeva, A. Serganov, S. Cai, J. Balatoni, R. Blasberg and J. Gelovani: “Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice”, Cancer Res., Vol. 64, (2004), pp. 6101–6108.PubMedCrossRefGoogle Scholar
  49. [49]
    Y. Kang, W. He, S. Tulley, G.P. Gupta, I. Serganova, C.R. Chen, K. Manova-Todorova, R. Blasberg, W.L. Gerald and J. Massague: “Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway”, Proc. Natl. Acad. Sci. U.S.A., Vol. 102, (2005), pp. 13909–13914.PubMedCrossRefGoogle Scholar
  50. [50]
    P. Mayer-Kuckuk, M. Doubrovin, N.J. Gusani, T. Gade, J. Balatoni, T. Akhurst, R. Finn, Y. Fong, J.A. Koutcher, S. Larson, R. Blasberg, J.G. Tjuvajev, J.R. Bertino and D. Banerjee: “Imaging of dihydrofolate reductase fusion gene expression in xenografts of human liver metastases of colorectal cancer in living rats”, Eur. J. Nucl. Med. Mol. Imaging., Vol. 30, (2003), pp. 1281–1291.PubMedCrossRefGoogle Scholar
  51. [51]
    P. Mayer-Kuckuk, D. Banerjee, S. Malhotra, M. Doubrovin, M. Iwamoto, T. Akhurst, J. Balatoni, W. Bornmann, R. Finn, S. Larson, Y. Fong, J. Gelovani Tjuvajev, R. Blasberg and J.R. Bertino: “Cells exposed to antifolates show increased cellular levels of proteins fused to dihydrofolate reductase:a method to modulate gene expression”, Proc. Natl. Acad. Sci. U.S.A., Vol. 99, (2002), pp. 3400–3405.PubMedCrossRefGoogle Scholar
  52. [52]
    A.H. Gobuty, R.G. Robinson and R.F. Barth: “Organ distribution of 99mTc-and 51Cr-labeled autologous peripheral blood lymphocytes in rabbits”, J. Nucl. Med., Vol. 18, (1977), pp. 141–146.PubMedGoogle Scholar
  53. [53]
    C.K. Papierniak, R.E. Bourey, R.R. Kretschmer, S.P. Gotoff and L.G. Colombetti: “Technetium-99m labeling of human monocytes for chemotactic studies”, J. Nucl. Med., Vol. 17, (1976), pp. 988–992.PubMedGoogle Scholar
  54. [54]
    J. Korf, L. Veenma-van der Duin, R. Brinkman-Medema, A. Niemarkt and L.F. de Leij: “Divalent cobalt as a label to study lymphocyte distribution using PET and SPECT”, J. Nucl. Med., Vol. 39, (1998), pp. 836–841.PubMedGoogle Scholar
  55. [55]
    G.H. Rannie, M.L. Thakur and W.L. Ford: “An experimental comparison of radioactive labels with potential application to lymphocyte migration studies in patients”, Clin. Exp. Immunol., Vol. 29, (1977), pp. 509–514.PubMedGoogle Scholar
  56. [56]
    N. Adonai, K.N. Nguyen, J. Walsh, M. Iyer, T. Toyokuni, M.E. Phelps, T. Mc-Carthy, D.W. McCarthy and S.S. Gambhir: “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., Vol. 99, (2002), pp. 3030–3035.PubMedCrossRefGoogle Scholar
  57. [57]
    A.B. Hagani, I. Riviere, C. Tan, A. Krause and M. Sadelain: “Activation conditions determine susceptibility of murine primary T-lymphocytes to retroviral infection”, J. Gene Med., Vol. 1, (1999), pp. 341–351.PubMedCrossRefGoogle Scholar
  58. [58]
    H.F. Gallardo, C. Tan, D. Ory and M. Sadelain: “Recombinant retroviruses pseudo-typed with the vesicular stomatitis virus G glycoprotein mediate both stable gene transfer and pseudotransduction in human peripheral blood lymphocytes”, Blood, Vol. 90, (1997), pp. 952–957.PubMedGoogle Scholar
  59. [59]
    C.M. Rooney, C.A. Smith, C.Y. Ng, S. Loftin, C. Li, R.A. Krance, M.K. Brenner and H.E. Heslop: “Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation”, Lancet, Vol. 345, (1995), pp. 9–13.PubMedCrossRefGoogle Scholar
  60. [60]
    S. Verzeletti, C. Bonini, S. Marktel, N. Nobili, F. Ciceri, C. Traversari and C. Bordignon: “Herpes simplex virus thymidine kinase gene transfer for controlled graft-versus-host disease and graft-versus-leukemia: clinical follow-up and improved new vectors”, Hum. Gene Ther., Vol. 9, (1998), pp. 2243–2251.PubMedGoogle Scholar
  61. [61]
    C. Bonini, G. Ferrari, S. Verzeletti, P. Servida, E. Zappone, L. Ruggieri, M. Ponzoni, S. Rossini, F. Mavilio, C. Traversari and C. Bordignon: “HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia”, Science, Vol. 276, (1997), pp. 1719–1724.PubMedCrossRefGoogle Scholar
  62. [62]
    J. Hardy, M. Edinger, M.H. Bachmann, R.S. Negrin, C.G. Fathman and C.H. Contag: “Bioluminescence imaging of lymphocyte trafficking in vivo”, Exp. Hematol., Vol. 29, (2001), pp. 1353–1360.PubMedCrossRefGoogle Scholar
  63. [63]
    W. Zhang, J.Q. Feng, S.E. Harris, P.R. Contag, D.K. Stevenson and C.H. Contag: “Rapid in vivo functional analysis of transgenes in mice using whole body imaging of luciferase expression”, Transgenic Res, Vol. 10, (2001), pp. 423–434.PubMedCrossRefGoogle Scholar
  64. [64]
    G. Koehne, M. Doubrovin, E. Doubrovina, P. Zanzonico, H.F. Gallardo, A. Ivanova, J. Balatoni, J. Teruya-Feldstein, G. Heller, C. May, V. Ponomarev, S. Ruan, R. Finn, R.G. Blasberg, W. Bornmann, I. Riviere, M. Sadelain, R.J. O’Reilly, S.M. Larson and J.G. Tjuvajev: “Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes”, Nat. Biotechnol., Vol. 21, (2003), pp. 405–413.PubMedCrossRefGoogle Scholar
  65. [65]
    G. Dai, O. Levy and N. Carrasco: “Cloning and characterization of the thyroid iodide transporter”, Nature, Vol. 379, (1996), pp. 458–460.PubMedCrossRefGoogle Scholar
  66. [66]
    S. Selmi-Ruby, C. Watrin, S. Trouttet-Masson, F. Bernier-Valentin, V. Flachon, Y. Munari-Silem and B. Rousset: “The porcine sodium/iodide symporter gene exhibits an uncommon expression pattern related to the use of alternative splice sites not present in the human or murine species”, Endocrinology, Vol. 144, (2003), pp. 1074–1085.PubMedCrossRefGoogle Scholar
  67. [67]
    U.H. Tazebay, I.L. Wapnir, O. Levy, O. Dohan, L.S. Zuckier, Q.H. Zhao, H.F. Deng, P.S. Amenta, S. Fineberg, R.G. Pestell and N. Carrasco: “The mammary gland iodide transporter is expressed during lactation and in breast cancer”, Nat. Med., Vol. 6, (2000), pp. 871–878.PubMedCrossRefGoogle Scholar
  68. [68]
    S. Eskandari, D.D. Loo, G. Dai, O. Levy, E.M. Wright and N. Carrasco: “Thyroid Na+/I-symporter. Mechanism, stoichiometry and specificity”, J. Biol. Chem., Vol. 272, (1997), pp. 27230–27238.PubMedCrossRefGoogle Scholar
  69. [69]
    J. Van Sande, C. Massart, R. Beauwens, A. Schoutens, S. Costagliola, J.E. Dumont and J. Wolff: “Anion selectivity by the sodium iodide symporter”, Endocrinology, Vol. 144, (2003), pp. 247–252.PubMedCrossRefGoogle Scholar
  70. [70]
    J. Che, M. Doubrovin, I. Serganova, L. Ageyeva, P. Zanzonico and R. Blasberg: “hNIS-IRES-eGFP dual reporter gene imaging”, Mol. Imaging, Vol. 4, (2005), pp. 128–136.PubMedGoogle Scholar
  71. [71]
    H. Kakinuma, E.R. Bergert, C. Spitzweg, J.C. Cheville, M.M. Lieber and J.C. Morris: “Probasin promoter (ARR(2)PB)-driven, prostate-specific expression of the human sodium iodide symporter (h-NIS) for targeted radioiodine therapy of prostate cancer”, Cancer Res., Vol. 63, (2003), pp. 7840–7844.PubMedGoogle Scholar
  72. [72]
    M.L. Schipper, A. Weber, M. Behe, R. Goke, W. Joba, H. Schmidt, T. Bert, B. Simon, R. Arnold, A.E. Heufelder and T.M. Behr: “Radioiodide treatment after sodium iodide symporter gene transfer is a highly effective therapy in neuroen-docrine tumor cells”, Cancer Res., Vol. 63, (2003), pp. 1333–1338.PubMedGoogle Scholar
  73. [73]
    D. Dingli, K.W. Peng, M.E. Harvey, P.R. Greipp, M.K. O’Connor, R. Cattaneo, J.C. Morris and S.J. Russell: “Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter”, Blood, Vol. 103, (2004), pp. 1641–1646.PubMedCrossRefGoogle Scholar
  74. [74]
    M. Huang, R.K. Batra, T. Kogai, Y.Q. Lin, J.M. Hershman, A. Lichtenstein, S. Sharma, L.X. Zhu, G.A. Brent and S.M. Dubinett: “Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non-small cell lung cancer”, Cancer Gene Ther., Vol. 8, (2001), pp. 612–618.PubMedCrossRefGoogle Scholar
  75. [75]
    D. Dingli, R.M. Diaz, E.R. Bergert, M.K. O’Connor, J.C. Morris and S.J. Russell: “Genetically targeted radiotherapy for multiple myeloma”, Blood, Vol. 102, (2003), pp. 489–496.PubMedCrossRefGoogle Scholar
  76. [76]
    D.J. Buchsbaum, T.R. Chaudhuri and K.R. Zinn: “Radiotargeted gene therapy”, J. Nucl. Med., Vol. 46(Suppl. 1), (2005), pp. 179S–186S.PubMedGoogle Scholar
  77. [77]
    D.J. Buchsbaum and D.T. Curiel: “Gene therapy for the treatment of cancer”, Cancer Biother. Radiopharm., Vol. 16, (2001), pp. 275–288.PubMedCrossRefGoogle Scholar
  78. [78]
    M. Miyagawa, M. Beyer, B. Wagner, M. Anton, C. Spitzweg, B. Gansbacher, M. Schwaiger and F.M. Bengel: “Cardiac reporter gene imaging using the human sodium/iodide symporter gene”, Cardiovasc. Res., Vol. 65, (2005), pp. 195–202.PubMedCrossRefGoogle Scholar
  79. [79]
    K.I. Kim, J.K. Chung, J.H. Kang, Y.J. Lee, J.H. Shin, H.J. Oh, J.M. Jeong, D.S. Lee and M.C. Lee: “Visualization of endogenous p53-mediated transcription in vivo using sodium iodide symporter”, Clin. Cancer Res”,, Vol. 11, (2005), pp. 123–128.PubMedGoogle Scholar
  80. [80]
    J. Faivre, J. Clerc, R. Gerolami, J. Herve, M. Longuet, B. Liu, J. Roux, F. Moal, M. Perricaudet and C. Brechot: “Long-term radioiodine retention and regression of liver cancer after sodium iodide symporter gene transfer in wistar rats”, Cancer Res, Vol. 64, (2004), pp. 8045–8051.PubMedCrossRefGoogle Scholar
  81. [81]
    K.H. Lee, H.K. Kim, J.Y. Paik, T. Matsui, Y.S. Choe, Y. Choi and B.T. Kim: “Accuracy of myocardial sodium/iodide symporter gene expression imaging with radioiodide: evaluation with a dual-gene adenovirus vector”, J. Nucl. Med., Vol. 46, (2005), pp. 652–657.PubMedGoogle Scholar
  82. [82]
    J.H. Shin, J.K. Chung, J.H. Kang, Y.J. Lee, K.I. Kim, Y. So, J.M. Jeong, D.S. Lee and M.C. Lee: “Noninvasive imaging for monitoring of viable cancer cells using a dual-imaging reporter gene”, J. Nucl. Med., Vol. 45, (2004), pp. 2109–2115.PubMedGoogle Scholar
  83. [83]
    M.K. So, J.H. Kang, J.K. Chung, Y.J. Lee, J.H. Shin, K.I. Kim, J.M. Jeong, D.S. Lee and M.C. Lee: “In vivo imaging of retinoic acid receptor activity using a sodium/iodide symporter and luciferase dual imaging reporter gene”, Mol. Imaging, Vol. 3, (2004), pp. 163–171.PubMedCrossRefGoogle Scholar
  84. [84]
    J.H. Kang, D.S. Lee, J.C. Paeng, J.S. Lee, Y.H. Kim, Y.J. Lee, W. Hwang Do, J.M. Jeong, S.M. Lim, J.K. Chung and M.C. Lee: “Development of a sodium/iodide symporter (NIS)-transgenic mouse for imaging of cardiomyocyte-specific reporter gene expression”, J. Nucl. Med., Vol. 46, (2005), pp. 479–483.PubMedGoogle Scholar
  85. [85]
    R. Buursma, A.M. Beerens, E.F. de Vries, A. van Waarde, M.G. Rots, G.A. Hospers, W. Vaalburg and H.J. Haisma: “The Human Norepinephrine Transporter in Combination with 11C-m-Hydroxyephedrine as a Reporter Gene/Reporter Probe for PET of Gene Therapy”, J. Nucl. Med., Vol. 46, (2005), pp. 2068–2075.PubMedGoogle Scholar
  86. [86]
    Altmann, M. Kissel, S. Zitzmann, W. Kubler, M. Mahmut, P. Peschke and U. Haberkorn: “Increased MIBG uptake after transfer of the human norepinephrine transporter gene in rat hepatoma”, J. Nucl. Med., Vol. 44, (2003), pp. 973–980.PubMedGoogle Scholar
  87. [87]
    T. Pacholczyk, R.D. Blakely and S.G. Amara: “Expression cloning of a cocaine-and antidepressant-sensitive human noradrenaline transporter”, Nature, Vol. 350, (1991), pp. 350–354.PubMedCrossRefGoogle Scholar
  88. [88]
    S. Kitayama, T. Ikeda, C. Mitsuhata, T. Sato, K. Morita and T. Dohi: “Dominant negative isoform of rat norepinephrine transporter produced by alternative RNA splicing”, J. Biol. Chem., Vol. 274, (1999), pp. 10731–10736.PubMedCrossRefGoogle Scholar
  89. [89]
    J.D. Fritz, L.D. Jayanthi, M.A. Thoreson and R.D. Blakely: “Cloning and chromosomal mapping of the murine norepinephrine transporter”, J. Neurochem., Vol. 70, (1998), pp. 2241–2251.PubMedCrossRefGoogle Scholar
  90. [90]
    M. Bruss, J. Kunz, B. Lingen and H. Bonisch: “Chromosomal mapping of the human gene for the tricyclic antidepressant-sensitive noradrenaline transporter”, Hum. Genet., Vol. 91, (1993), pp. 278–280.PubMedGoogle Scholar
  91. [91]
    P. Porzgen, H. Bonisch and M. Bruss: “Molecular cloning and organization of the coding region of the human norepinephrine transporter gene”, Biochem. Biophys. Res. Commun., Vol. 215, (1995), pp. 1145–1150.PubMedCrossRefGoogle Scholar
  92. [92]
    P. Porzgen, H. Bonisch and M. Bruss: “Molecular cloning and organization of the coding region of the human norepinephrine transporter gene”, Biochem. Biophys. Res. Commun., Vol. 227, (1996), pp. 642–643.PubMedCrossRefGoogle Scholar
  93. [93]
    B. Lingen, M. Bruss and H. Bonisch: “Cloning and expression of the bovine sodium-and chloride-dependent noradrenaline transporter”, FEBS Lett., Vol. 342, (1994), pp. 235–238.PubMedCrossRefGoogle Scholar
  94. [94]
    L.D. Burton, A.G. Kippenberger, B. Lingen, M. Bruss, H. Bonisch and D.L. Christie: “A variant of the bovine noradrenaline transporter reveals the importance of the C-terminal region for correct targeting to the membrane and functional expression”, Biochem. J., Vol. 330(Pt 2), (1998), pp. 909–914.PubMedGoogle Scholar
  95. [95]
    S. Kitayama, K. Morita and T. Dohi: “Functional characterization of the splicing variants of human norepinephrine transporter”, Neurosci. Lett., Vol. 312, (2001), pp. 108–112.PubMedCrossRefGoogle Scholar
  96. [96]
    Y. Zhao and L. Sun: “Perinatal cocaine exposure reduces myocardial norepinephrine transporter function in the neonatal rat”, Neurotoxicol. Teratol., Vol. 26, (2004), pp. 443–450.PubMedCrossRefGoogle Scholar
  97. [97]
    G. Eisenhofer: “The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines”, Pharmacol. Ther., Vol. 91, (2001), pp. 35–62.PubMedCrossRefGoogle Scholar
  98. [98]
    O. Langer, F. Dolle, H. Valette, C. Halldin, F. Vaufrey, C. Fuseau, C. Coulon, M. Ottaviani, K. Nagren, M. Bottlaender, B. Maziere and C. Crouzel: “Synthesis of high-specific-radioactivity 4-and 6-[18F]fluorometaraminol-PET tracers for the adrenergic nervous system of the heart”, Bioorg. Med. Chem., Vol. 9, (2001), pp. 677–694.PubMedCrossRefGoogle Scholar
  99. [99]
    M. Wieland, J. Wu, L.E. Brown, T.J. Mangner, D.P. Swanson and W.H. Beierwaltes: “Radiolabeled adrenergi neuron-blocking agents: adrenomedullary imaging with [131I]iodobenzylguanidine”, J. Nucl. Med., Vol. 21, (1980), pp. 349–353.PubMedGoogle Scholar
  100. [100]
    R. Wafelman, C.A. Hoefnagel, R.A. Maes and J.H. Beijnen: “Radioiodinated metaiodobenzylguanidine: a review of its biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry”, Eur. J. Nucl. Med., Vol. 21, (1994), pp. 545–559.PubMedCrossRefGoogle Scholar
  101. [101]
    M. Anton, B. Wagner, R. Haubner, C. Bodenstein, B.E. Essien, H. Bonisch, M. Schwaiger, B. Gansbacher and W.A. Weber: “Use of the norepinephrine transporter as a reporter gene for non-invasive imaging of genetically modified cells”, J. Gene Med., Vol. 6, (2004), pp. 119–126.PubMedCrossRefGoogle Scholar
  102. [102]
    J.V. Glowniak, J.E. Kilty, S.G. Amara, B.J. Hoffman and F.E. Turner: “Evaluation of metaiodobenzylguanidine uptake by the norepinephrine, dopamine and serotonin transporters”, J. Nucl. Med., Vol. 34, (1993), pp. 1140–1146.PubMedGoogle Scholar
  103. [103]
    M. Boyd, S.H. Cunningham, M.M. Brown, R.J. Mairs and T.E. Wheldon: “Noradrenaline transporter gene transfer for radiation cell kill by 131I meta-iodobenzylguanidine”, Gene Ther., Vol. 6, (1999), pp. 1147–1152.PubMedCrossRefGoogle Scholar
  104. [104]
    H.E. Melikian, S. Ramamoorthy, C.G. Tate and R.D. Blakely: “Inability to N-glycosylate the human norepinephrine transporter reduces protein stability, surface trafficking and transport activity but not ligand recognition”, Mol. Pharmacol., Vol. 50, (1996), pp. 266–276.PubMedGoogle Scholar
  105. [105]
    S. Shouda, C. Kurata, T. Mikami and Y. Wakabayashi: “Effects of extrinsically elevated plasma norepinephrine concentration on myocardial 123I-MIBG kinetics in rats”, J. Nucl. Med., Vol. 40, (1999), pp. 2088–2093.PubMedGoogle Scholar
  106. [106]
    P.C. Wang, N.T. Buu, O. Kuchel and J. Genest: “Conjugation patterns of endogenous plasma catecholamines in human and rat: “A new specific method for analysis of glucuronide-conjugated catecholamines”, J. Lab. Clin. Med., Vol. 101, (1983), pp. 141–151.PubMedGoogle Scholar
  107. [107]
    O. Kifor, F.D. Moore Jr., M. Delaney, J. Garber, G.N. Hendy, R. Butters, P. Gao, T.L. Cantor, I. Kifor, E.M. Brown and J. Wysolmerski: “A syndrome of hypocalciuric hypercalcemia caused by autoantibodies directed at the calcium-sensing receptor”, J. Clin. Endocrinol. Metab., Vol. 88, (2003), pp. 60–72.PubMedCrossRefGoogle Scholar
  108. [108]
    K.C. Allman, D.M. Wieland, O. Muzik, T.R. Degrado, E.R. Wolfe Jr. and M. Schwaiger: “Carbon-11 hydroxyephedrine with positron emission tomography for serial assessment of cardiac adrenergic neuronal function after acute myocardial infarction in humans”, J. Am. Coll. Cardiol., Vol. 22, (1993), pp. 368–375.PubMedCrossRefGoogle Scholar
  109. [109]
    Trampal, H. Engler, C. Juhlin, M. Bergstrom and B. Langstrom: “Pheochromocytomas: detection with 11C hydroxyephedrine PET”, Radiology, Vol. 230, (2004), pp. 423–428.PubMedGoogle Scholar
  110. [110]
    L. Krulich, A.P. Dhariwal and S.M. McCann: “Stimulatory and inhibitory effects of purified hypothalamic extracts on growth hormone release from rat pituitary in vitro”, Endocrinology, Vol. 83, (1968), pp. 783–790.PubMedCrossRefGoogle Scholar
  111. [111]
    P. Brazeau, W. Vale, R. Burgus, N. Ling, M. Butcher, J. Rivier and R. Guillemin: “Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone”, Science, Vol. 179, (1973), pp. 77–79.PubMedGoogle Scholar
  112. [112]
    S. Reichlin: “Somatostatin”, N. Engl. J. Med., Vol. 309, (1983), pp. 1495–1501.PubMedCrossRefGoogle Scholar
  113. [113]
    J.C. Reubi, L. Kvols, E. Krenning and S.W. Lamberts: “Distribution of somatostatin receptors in normal and tumor tissue”, Metabolism, Vol. 39, (1990), pp. 78–81.PubMedCrossRefGoogle Scholar
  114. [114]
    W. Bauer, U. Briner, W. Doepfner, R. Haller, R. Huguenin, P. Marbach, T.J. Petcher and Pless: “SMS 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action”, Life Sci., Vol. 31, (1982), pp. 1133–1140.PubMedCrossRefGoogle Scholar
  115. [115]
    K.P. Eisenwiener, M.I. Prata, I. Buschmann, H.W. Zhang, A.C. Santos, S. Wenger, J.C. Reubi and H.R. Macke: “NODAGATOC, a new chelator-coupled somatostatin analogue labeled with [67/68Ga] and [111In] for SPECT, PET and targeted therapeutic applications of somatostatin receptor (hsst2) expressing tumors”, Bioconjug. Chem., Vol. 13, (2002), pp. 530–541.PubMedCrossRefGoogle Scholar
  116. [116]
    Y. Menda and D. Kahn: “Somatostatin receptor imaging of non-small cell lung cancer with 99mTc depreotide”, Semin. Nucl. Med., Vol. 32, (2002), pp. 92–96.PubMedCrossRefGoogle Scholar
  117. [117]
    K.R. Zinn, D.J. Buchsbaum, T.R. Chaudhuri, J.M. Mountz, W.E. Grizzle and B.E. Rogers: “Noninvasive monitoring of gene transfer using a reporter receptor imaged with a high-affinity peptide radiolabeled with 99mTc or 188Re”, J. Nucl. Med., Vol. 41, (2000), pp. 887–895.PubMedGoogle Scholar
  118. [118]
    B.E. Rogers, J.J. Parry, R. Andrews, P. Cordopatis, B.A. Nock and T. Maina: “MicroPET Imaging of Gene Transfer with a Somatostatin Receptor-Based Reporter Gene and 94mTc-Demotate 1”, J. Nucl. Med., Vol. 46, (2005), pp. 1889–1897.PubMedGoogle Scholar
  119. [119]
    R. Sibley and F.J. Monsma Jr.: “Molecular biology of dopamine receptors”, Trends Pharmacol. Sci., Vol. 13, (1992), pp. 61–69.PubMedCrossRefGoogle Scholar
  120. [120]
    J.R. Bunzow, H.H. Van Tol, D.K. Grandy, P. Albert, J. Salon, M. Christie, C.A. Machida, K.A. Neve and O. Civelli: “Cloning and expression of a rat D2 dopamine receptor cDNA”, Nature, Vol. 336, (1988), pp. 783–787.PubMedCrossRefGoogle Scholar
  121. [121]
    N. Satyamurthy, J.R. Barrio, G.T. Bida, S.C. Huang, J.C. Mazziotta and M.E. Phelps: “3-(2′-[18F]fluoroethyl)spiperone, a potent dopamine antagonist: synthesis, structural analysis and in-vivo utilization in humans”, Int. J. Rad. Appl. Instrum. A, Vol. 41, (1990), pp. 113–129.PubMedCrossRefGoogle Scholar
  122. [122]
    J.R. Barrio, N. Satyamurthy, S.C. Huang, R.E. Keen, C.H. Nissenson, J.M. Hoffman, R.F. Ackermann, M.M. Bahn, J.C. Mazziotta and M.E. Phelps: “3-(2′-[18F]fluoroethyl)spiperone: in vivo biochemical and kinetic characterization in rodents, nonhuman primates and humans”, J. Cereb. Blood Flow Metab. Vol. 9, (1989), pp. 830–839.PubMedGoogle Scholar
  123. [123]
    D.C. MacLaren, S.S. Gambhir, N. Satyamurthy, J.R. Barrio, S. Sharfstein, T. Toyokuni, L. Wu, A.J. Berk, S.R. Cherry, M.E. Phelps and H.R. Herschman: “Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals”, Gene Ther., Vol. 6, (1999), pp. 785–791.PubMedCrossRefGoogle Scholar
  124. [124]
    Q. Liang, N. Satyamurthy, J.R. Barrio, T. Toyokuni, M.P. Phelps, S.S. Gambhir and H.R. Herschman: “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., Vol. 8, (2001), pp. 1490–1498.PubMedCrossRefGoogle Scholar
  125. [125]
    Y. Chen, J.C. Wu, J.J. Min, G. Sundaresan, X. Lewis, Q. Liang, H.R. Herschman and S.S. Gambhir: “Micro-positron emission tomography imaging of cardiac gene expression in rats using bicistronic adenoviral vector-mediated gene delivery”, Circulation, Vol. 109, (2004), pp. 1415–1420.PubMedCrossRefGoogle Scholar
  126. [126]
    J.C. Wu, M. Inubushi, G. Sundaresan, H.R. Schelbert and S.S. Gambhir: “Optical imaging of cardiac reporter gene expression in living rats”, Circulation, Vol. 105, (2002), pp. 1631–1634.PubMedCrossRefGoogle Scholar
  127. [127]
    J. Minn, Y. Kang, I. Serganova, G.P. Gupta, D.D. Giri, M. Doubrovin, V. Ponomarev, W.L. Gerald, R. Blasberg and J. Massague: “Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors”, J. Clin. Invest., Vol. 115, (2005), pp. 44–55.PubMedCrossRefGoogle Scholar
  128. [128]
    T. Wilson and J.W. Hastings: “Bioluminescence”, Annu. Rev. Cell Dev. Biol., Vol. 14, (1998), pp. 197–230.PubMedCrossRefGoogle Scholar
  129. [129]
    Y.A. Yu, T. Timiryasova, Q. Zhang, R. Beltz and A.A. Szalay: “Optical imaging: bacteria, viruses and mammalian cells encoding light-emitting proteins reveal the locations of primary tumors and metastases in animals”, Anal. Bioanal. Chem. Vol. 377, (2003), pp. 964–972.PubMedCrossRefGoogle Scholar
  130. [130]
    J.C. Matthews, K. Hori and M.J. Cormier: “Purification and properties of Renilla reniformis luciferase”, Biochemistry, Vol. 16, (1977), pp. 85–91.PubMedCrossRefGoogle Scholar
  131. [131]
    J.E. Wampler, K. Hori, J.W. Lee and M.J. Cormier: “Structured bioluminescence. Two emitters during both the in vitro and the in vivo bioluminescence of the sea pansy, Renilla”, Biochemistry, Vol. 10, (1971), pp. 2903–2909.PubMedCrossRefGoogle Scholar
  132. [132]
    B.A. Tannous, D.E. Kim, J.L. Fernandez, R. Weissleder and X.O. Breakefield: “Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo”, Mol. Ther., Vol. 11, (2005), pp. 435–443.PubMedCrossRefGoogle Scholar
  133. [133]
    M. Verhaegent and T.K. Christopoulos: “Recombinant Gaussia luciferase. Over-expression, purification and analytical application of a bioluminescent reporter for DNA hybridization”, Anal. Chem., Vol. 74, (2002), pp. 4378–4385.PubMedCrossRefGoogle Scholar
  134. [134]
    L.F. Greer III and A.A. Szalay: “Imaging of light emission from the expression of luciferases in living cells and organisms: a review”, Luminescence, Vol. 17, (2002), pp. 43–74.PubMedCrossRefGoogle Scholar
  135. [135]
    E.A. Meighen: “Bacterial bioluminescence: organization, regulation and application of the lux genes”, FASEB J., Vol. 7, (1993), pp. 1016–1022.PubMedGoogle Scholar
  136. [136]
    S. Bhaumik and S.S. Gambhir: “Optical imaging of Renilla luciferase reporter gene expression in living mice”, Proc. Natl. Acad. Sci. U.S.A., Vol. 99, (2002), pp. 377–382.PubMedCrossRefGoogle Scholar
  137. [137]
    H. Zhao, T.C. Doyle, R.J. Wong, Y. Cao, D.K. Stevenson, D. Piwnica-Worms and C.H. Contag: “Characterization of coelenterazine analogs for measurements of Renilla luciferase activity in live cells and living animals”, Mol. Imaging, Vol. 3, (2004), pp. 43–54.PubMedCrossRefGoogle Scholar
  138. [138]
    A. Pichler, J.L. Prior and D. Piwnica-Worms: “Imaging reversal of multidrug resistance in living mice with bioluminescence: MDR1 P-glycoprotein transports coelenterazine”, Proc. Natl. Acad. Sci. U.S.A., Vol. 101, (2004), pp. 1702–1707.PubMedCrossRefGoogle Scholar
  139. [139]
    J.R. de Wet, K.V. Wood, M. DeLuca, D.R. Helinski and S. Subramani: “Firefly luciferase gene: structure and expression in mammalian cells”, Mol. Cell. Biol., Vol. 7, (1987), pp. 725–737.PubMedGoogle Scholar
  140. [140]
    H. Zhao, T.C. Doyle, O. Coquoz, F. Kalish, B.W. Rice and C.H. Contag: “Emission spectra of bioluminescent reporters and interaction with mammalian tissue determine the sensitivity of detection in vivo”, J. Biomed. Opt., Vol. 10, (2005), pp. 41210.PubMedCrossRefGoogle Scholar
  141. [141]
    M.V. Matz, A.F. Fradkov, Y.A. Labas, A.P. Savitsky, A.G. Zaraisky, M.L. Markelov and S.A. Lukyanov: “Fluorescent proteins from nonbioluminescent Anthozoa species”, Nat. Biotechnol. Vol. 17, (1999), pp. 969–973.PubMedCrossRefGoogle Scholar
  142. [142]
    M.M. Falk and U. Lauf: “High resolution, fluorescence deconvolution microscopy and tagging with the autofluorescent tracers CFP, GFP and YFP to study the structural composition of gap junctions in living cells”, Microsc. Res. Tech., Vol. 52, (2001), pp. 251–262.PubMedCrossRefGoogle Scholar
  143. [143]
    K. Hadjantonakis and A. Nagy: “The color of mice: in the light of GFP-variant reporters”, Histochem. Cell Biol., Vol. 115, (2001), pp. 49–58.PubMedGoogle Scholar
  144. [144]
    Y.A. Labas, N.G. Gurskaya, Y.G. Yanushevich, A.F. Fradkov, K.A. Lukyanov, S.A. Lukyanov and M.V. Matz: “Diversity and evolution of the green fluorescent protein family”, Proc. Natl. Acad. Sci. U.S.A., Vol. 99, (2002), pp. 4256–4261.PubMedCrossRefGoogle Scholar
  145. [145]
    R. Yuste: “Fluorescence microscopy today”, Nat. Methods, Vol. 2, (2005), pp. 902–904.PubMedCrossRefGoogle Scholar
  146. [146]
    D.M. Chudakov, S. Lukyanov and K.A. Lukyanov: “Fluorescent proteins as a toolkit for in vivo imaging”, Trends Biotechnol., Vol. 23, (2005), pp. 605–613.PubMedCrossRefGoogle Scholar
  147. [147]
    D.A. Shagin, E.V. Barsova, Y.G. Yanushevich, A.F. Fradkov, K.A. Lukyanov, Y.A. Labas, T.N. Semenova, J.A. Ugalde, A. Meyers, J.M. Nunez, E.A. Widder, S.A. Lukyanov and M.V. Matz: “GFP-like proteins as ubiquitous metazoan superfamily: evolution of functional features and structural complexity”, Mol. Biol. Evol., Vol. 21, (2004), pp. 841–850.PubMedCrossRefGoogle Scholar
  148. [148]
    J. Wiedenmann, A. Schenk, C. Rocker, A. Girod, K.D. Spindler and G.U. Nienhaus: “A far-red fluorescent protein with fast maturation and reduced oligomerization tendency from Entacmaea quadricolor (Anthozoa, Actinaria)”, Proc. Natl. Acad. Sci. U.S.A., Vol. 99, (2002), pp. 11646–11651.PubMedCrossRefGoogle Scholar
  149. [149]
    N.G. Gurskaya, A.F. Fradkov, A. Terskikh, M.V. Matz, Y.A. Labas, V.I. Martynov, Y.G. Yanushevich, K.A. Lukyanov and S.A. Lukyanov: “GFP-like chromoproteins as a source of far-red fluorescent proteins”, FEBS Lett.Vol. 507, (2001), pp. 16–20.PubMedCrossRefGoogle Scholar
  150. [150]
    R.E. Campbell, O. Tour, A.E. Palmer, P.A. Steinbach, G.S. 1 Baird, D.A. Zacharias and R.Y. Tsien: “A monomeric red fluorescent protein”, Proc. Natl. Acad. Sci. U.S.A., Vol. 99, (2002), pp. 7877–7882.PubMedCrossRefGoogle Scholar
  151. [151]
    L. Wang, W.C. Jackson, P.A. Steinbach and R.Y. Tsien: “Evolution of new nonantibody proteins via iterative somatic hypermutation”, Proc. Natl. Acad. Sci. U.S.A., Vol. 101, (2004), pp. 16745–16749.PubMedCrossRefGoogle Scholar
  152. [152]
    D.M. Chudakov, V.V. Verkhusha, D.B. Staroverov, E.A. Souslova, S. Lukyanov and K.A. Lukyanov: “Photoswitchable cyan fluorescent protein for protein tracking”, Nat. Biotechnol. Vol. 22, (2004), pp. 1435–1439.PubMedCrossRefGoogle Scholar
  153. [153]
    D.M. Chudakov, V.V. Belousov, A.G. Zaraisky, V.V. Novoselov, D.B. Staroverov, D.B. Zorov, S. Lukyanov and K.A. Lukyanov: “Kindling fluorescent proteins for precise in vivo photolabeling”, Nat. Biotechnol. Vol. 21, (2003), pp. 191–194.PubMedCrossRefGoogle Scholar
  154. [154]
    D.M. Chudakov, A.V. Feofanov, N.N. Mudrik, S. Lukyanov and K.A. Lukyanov: “Chromophore environment provides clue to “kindling fluorescent protein”, riddle”, J. Biol. Chem. Vol. 278, (2003), pp. 7215–7219.PubMedCrossRefGoogle Scholar
  155. [155]
    J. Wiedenmann, S. Ivanchenko, F. Oswald, F. Schmitt, C. Rocker, A. Salih, K.D. Spindler and G.U. Nienhaus: “EosFP, a fluorescent marker protein with UV-inducible green-to-red fluorescence conversion”, Proc. Natl. Acad. Sci. U.S.A., Vol. 101, (2004), pp. 15905–15910.PubMedCrossRefGoogle Scholar
  156. [156]
    R. Ando, H. Mizuno and A. Miyawaki: “Regulated fast nucleocytoplasmic shuttling observed by reversible protein highlighting”, Science, Vol. 306, (2004), pp. 1370–1373.PubMedCrossRefGoogle Scholar
  157. [157]
    A. De and S.S. Gambhir: “Noninvasive imaging of protein-protein interactions from live cells and living subjects using bioluminescence resonance energy transfer”, FASEB J., Vol. 19, (2005), pp. 2017–2019.PubMedGoogle Scholar
  158. [158]
    S. Zhang, C. Ma and M. Chalfie: “Combinatorial marking of cells and organelles with reconstituted fluorescent proteins”, Cell, Vol. 119, (2004), pp. 137–144.PubMedCrossRefGoogle Scholar
  159. [159]
    R.M. Hoffman: “The multiple uses of fluorescent proteins to visualize cancer in vivo”, Nat. Rev. Cancer, Vol. 5, (2005), pp. 796–806.PubMedCrossRefGoogle Scholar
  160. [160]
    M. Yang, E. Baranov, P. Jiang, F.X. Sun, X.M. Li, L. Li, S. Hasegawa, M. Bouvet, M. Al-Tuwaijri, T. Chishima, H. Shimada, A.R. Moossa, S. Penman and R.M. Hoffman: “Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases”, Proc. Natl. Acad. Sci. U.S.A., Vol. 97, (2000), pp. 1206–1211.PubMedCrossRefGoogle Scholar
  161. [161]
    V.A. Kolb, E.V. Makeyev and A.S. Spirin: “Co-translational folding of an eukaryotic multidomain protein in a prokaryotic translation system”, J. Biol. Chem., Vol. 275, (2000), pp. 16597–16601.PubMedCrossRefGoogle Scholar
  162. [162]
    C. Andreatta, P. Nahreini, A.R. Hovland, B. Kumar, J. Edwards-Prasad and K.N. Prasad: “Use of short-lived green fluorescent protein for the detection of proteasome inhibition”, Biotechniques, Vol. 30, (2001), pp. 656–660.PubMedGoogle Scholar
  163. [163]
    H. Ben-Tekaya, K. Miura, R. Pepperkok and H.P. Hauri: “Live imaging of bidirectional traffic from the ERGIC”, J. Cell. Sci., Vol. 118, (2005), pp. 357–367.PubMedCrossRefGoogle Scholar
  164. [164]
    V. Ponomarev, M. Doubrovin, I. Serganova, J. Vider, A. Shavrin, T. Beresten, A. Ivanova, L. Ageyeva, V. Tourkova, J. Balatoni, W. Bornmann, R. Blasberg and J. Gelovani Tjuvajev: “A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent and nuclear noninvasive imaging”, Eur. J. Nucl. Med. Mol. Imaging, Vol. 31, (2004), pp. 740–751.PubMedCrossRefGoogle Scholar

Copyright information

© Central European Science Journals Warsaw and Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Inna Serganova
    • 1
  • Ekaterina Moroz
    • 1
  • Maxim Moroz
    • 1
  • Nagavarakishore Pillarsetty
    • 1
    • 3
  • Ronald Blasberg
    • 1
    • 2
  1. 1.Department of NeurologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department RadiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department Radiochemistry/Cyclotron Core FacilityMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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