Gene therapy imaging in patients for oncological applications

Supplement

Abstract

Thus far, traditional methods for evaluating gene transfer and expression have been shown to be of limited value in the clinical arena. Consequently there is a real need to develop new methods that could be repeatedly and safely performed in patients for such purposes. Molecular imaging techniques for gene expression monitoring have been developed and successfully used in animal models, but their sensitivity and reproducibility need to be tested and validated in human studies. In this review, we present the current status of gene therapy-based anticancer strategies and show how molecular imaging, and more specifically radionuclide-based approaches, can be used in gene therapy procedures for oncological applications in humans. The basis of gene expression imaging is described and specific uses of these non-invasive procedures for gene therapy monitoring illustrated. Molecular imaging of transgene expression in humans and evaluation of response to gene-based therapeutic procedures are considered. The advantages of molecular imaging for whole-body monitoring of transgene expression as a way to permit measurement of important parameters in both target and non-target organs are also analyzed. The relevance of this technology for evaluation of the necessary vector dose and how it can be used to improve vector design are also examined. Finally, the advantages of designing a gene therapy-based clinical trial with imaging fully integrated from the very beginning are discussed and future perspectives for the development of these applications outlined.

Keywords

Gene therapy Molecular imaging Radionuclide imaging Monitoring Transgene expression 

References

  1. 1.
    International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 2001;409:860–921Google Scholar
  2. 2.
    Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science 2001;291:1304–51CrossRefPubMedGoogle Scholar
  3. 3.
    Pfeifer A, Verma IM. Gene therapy: promises and problems. Annu Rev Genomics Hum Genet 2001;2:177–211CrossRefPubMedGoogle Scholar
  4. 4.
    Verma I, Somia N. Gene therapy—promises, problems and prospects. Nature 1997;389:239–42CrossRefPubMedGoogle Scholar
  5. 5.
    Mulligan RC. The basic science of gene therapy. Science 1993;260:926–93PubMedGoogle Scholar
  6. 6.
  7. 7.
    Edelstein ML, Abedi MR, Wixon J, Edelstein RMJ. Gene therapy clinical trials worldwide 1989–2004—an overview. Gene Med 2004;6:597–602CrossRefGoogle Scholar
  8. 8.
    El-Aneed A. An overview of current delivery systems in cancer gene therapy. J Control Release 2004;94 1:1–14CrossRefPubMedGoogle Scholar
  9. 9.
    Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med 2001;7:33–40CrossRefPubMedGoogle Scholar
  10. 10.
    Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genetics 2003;4:346–58CrossRefGoogle Scholar
  11. 11.
    Peñuelas I, Boan J, Marti-Climent JM, Sangro B, Mazzolini G, Prieto J, et al. PET and gene therapy: basic concepts and experimental approaches for in vivo gene expression imaging. Mol Imaging Biol 2004;6:225–38CrossRefPubMedGoogle Scholar
  12. 12.
    Nichol C, Kim EE. Molecular imaging and gene therapy. J Nucl Med 2001;42:1368–74PubMedGoogle Scholar
  13. 13.
    Larson SM, Tjuvajev J, Blasberg R. Triumph over mischance: a role for nuclear medicine in gene therapy. J Nucl Med 1997;38:1230–3PubMedGoogle Scholar
  14. 14.
    Haberkorn U, Mier W, Eisenhut M. Scintigraphic imaging of gene expression and gene transfer. Curr Med Chem 2005;12 7:779–94CrossRefPubMedGoogle Scholar
  15. 15.
    Bogdanov A, Weissleder R. In vivo imaging of gene delivery and expression. Trends Biotech 2002;20 8:S11–8CrossRefGoogle Scholar
  16. 16.
    Vogt Sionov RV, Haupt Y. The cellular response to p53: the decision between life and death. Oncogene 1999;18:6145–57CrossRefPubMedGoogle Scholar
  17. 17.
    Zeimet AG, Marth C. Why did p53 gene therapy fail in ovarian cancer? Lancet Oncol 2003;4 7:415–22CrossRefPubMedGoogle Scholar
  18. 18.
    Shen C, Rattat D, Buck A, Mehrke G, Polat B, Ribbert H, et al. Targeting bcl-2 by triplex-forming oligonucleotide—a promising carrier for gene-radiotherapy. Cancer Biother Radiopharm 2003;18 1:17–26CrossRefPubMedGoogle Scholar
  19. 19.
    Morishita R, Higaki J, Tomita N, Ogihara T. Application of transcription factor “decoy” strategy as means of gene therapy and study of gene expression in cardiovascular disease. Circ Res 1998;82:1023–8PubMedGoogle Scholar
  20. 20.
    Crooke ST. Antisense strategies. Curr Mol Med 2004;4 5:465–87Google Scholar
  21. 21.
    Bi F, Liu N, Fan D. Small interfering RNA: a new tool for gene therapy. Curr Gene Ther 2003;3 5:411–7CrossRefPubMedGoogle Scholar
  22. 22.
    Bagheri S, Kashani-Sabet M. Ribozymes in the age of molecular therapeutics. Curr Mol Med 2004;4 5:489–506CrossRefPubMedGoogle Scholar
  23. 23.
    Fillat C, Carrio M, Cascante A, Sangro B. Suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene/ganciclovir system: fifteen years of application. Curr Gene Ther 2003;3 1:13–26PubMedGoogle Scholar
  24. 24.
    Freeman SM, Abboud CN, Whartenby KA, Packman CH, Koeplin DS, Moolten FL, et al. The “bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res 1993;53 21:5274–83PubMedGoogle Scholar
  25. 25.
    van Dillen IJ, Mulder NH, Vaalburg W, de Vries EF, Hospers GA. Influence of the bystander effect on HSV-tk/GCV gene therapy. A review. Curr Gene Ther 2002;2 3:307–22PubMedGoogle Scholar
  26. 26.
    Ribas A, Butterfield LH, Economou JS. Genetic immunotherapy for cancer. Oncologist 2000;5 2:87–98CrossRefPubMedGoogle Scholar
  27. 27.
    Sangro B, Mazzolini G, Ruiz J, Herraiz M, Quiroga J, Herrero I, et al. Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors. J Clin Oncol 2004;22 8:1389–97CrossRefPubMedGoogle Scholar
  28. 28.
    Mazzolini G, Alfaro C, Sangro B, Feijoo E, Ruiz J, Benito A, et al. Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas. J Clin Oncol 2005;23 5:999–1010CrossRefPubMedGoogle Scholar
  29. 29.
    Hanke P, Serwe M, Dombrowski F, Sauerbruch T, Caselmann WH. DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice. Cancer Gene Ther 2002;9 4:346–55CrossRefPubMedGoogle Scholar
  30. 30.
    Isayeva T, Kumar S, Ponnazhagan S. Anti-angiogenic gene therapy for cancer (review). Int J Oncol 2004;25 2:335–43PubMedGoogle Scholar
  31. 31.
    Ntziachristos V, Bremer C, Graves EE, Ripoll J, Weissleder R. In vivo tomographic imaging of near-infrared fluorescent probes. Mol Imaging 2002;1 2:82–8CrossRefPubMedGoogle Scholar
  32. 32.
    Ntziachristos V, Tung CH, Bremer C, Weissleder R. Fluorescence molecular tomography resolves protease activity in vivo. Nat Med 2002;8 7:757–60CrossRefPubMedGoogle Scholar
  33. 33.
    Weissleder R, Moore A, Mahmood U, Bhorade R, Benveniste H, Chiocca EA, et al. In vivo magnetic resonance imaging of transgene expression. Nat Med 2000;6 3:351–5CrossRefPubMedGoogle Scholar
  34. 34.
    Genove G, DeMarco U, Xu H, Goins WF, Ahrens ET. A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 2005;11 4:450–4CrossRefPubMedGoogle Scholar
  35. 35.
    Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2002;2:683–93CrossRefPubMedGoogle Scholar
  36. 36.
    Phelps ME. PET: molecular imaging and its biological applications. Berlin Heidelberg New York: Springer; 2004Google Scholar
  37. 37.
    Chatziioannou AF. PET scanners dedicated to molecular imaging of small animal models. Mol Imaging Biol 2002;4 1:47–63CrossRefPubMedGoogle Scholar
  38. 38.
    Phelps ME. Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci U S A 2000;97 16:9226–33CrossRefPubMedGoogle Scholar
  39. 39.
    Yu Y, Annala AJ, Barrio JR, Toyokuni T, Satyamurthy N, Namavari M, et al. Quantification of target gene expression by imaging reporter gene expression in living animals. Nat Med 2000;6:933–7CrossRefPubMedGoogle Scholar
  40. 40.
    Sangro B, Qian C, Ruiz J, Prieto J. Tracing transgene expression in cancer gene therapy: a requirement for rational progress in the field. Mol Imaging Biol 2002;4:27–33CrossRefPubMedGoogle Scholar
  41. 41.
    Haberkorn U, Altmann A, Mier W, Eisenhut M. Impact of functional genomics and proteomics on radionuclide imaging. Semin Nucl Med 2004;34 1:4–22CrossRefGoogle Scholar
  42. 42.
    Gambhir SS, Barrio JR, Herschman HR, Phelps ME. Assays for noninvasive imaging of reporter gene expression. Nucl Med Biol 1999;26 5:481–90CrossRefPubMedGoogle Scholar
  43. 43.
    Gambhir SS, Barrio JR, Herschman HR, Phelps ME. Imaging gene expression: principles and assays. J Nucl Cardiol 1999;6 2:219–33Google Scholar
  44. 44.
    Haberkorn U, Oberdorfer F, Gebert J, Morr I, Haack K, Weber K, et al. Monitoring gene therapy with cytosine deaminase: in vitro studies using tritiated-5-fluorocytosine. J Nucl Med 1996;37:87–94PubMedGoogle Scholar
  45. 45.
    Haberkorn U, Altmann A, Morr I, Knopf KW, Germann C, Haeckel R, et al. Monitoring gene therapy with herpes simplex virus thymidine kinase in hepatoma cells: uptake of specific substrates. J Nucl Med 1997;38:287–94PubMedGoogle Scholar
  46. 46.
    Brust P, Haubner R, Friedrich A, Scheunemann M, Anton M, Koufaki ON, et al. Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression. Eur J Nucl Med 2001;28 6:721–9CrossRefPubMedGoogle Scholar
  47. 47.
    Jacobs A, Braunlich I, Graf R, Lercher M, Sakaki T, Voges J, et al. Quantitative kinetics of [124I]FIAU in cat and man. J Nucl Med 2001;42 3:467–75PubMedGoogle Scholar
  48. 48.
    Nanda D, de Jong M, Vogels R, Havenga M, Driesse M, Bakker W, et al. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU. Eur J Nucl Med Mol Imaging. 2002;29 7:939–47CrossRefPubMedGoogle Scholar
  49. 49.
    Tjuvajev JG, Doubrovin M, Akgurst T, Cai S, Balatoni J, Alauddin MM, et al. Comparison of radiolabeled nucleoside probes (FIAU; FHBG; FHPG) for PET imaging of HSV1-tk gene expression. J Nucl Med 2002;43 8:1072–83PubMedGoogle Scholar
  50. 50.
    Alauddin MM, Shahinian A, Gordon EM, Conti PS. Evaluation of 2′-deoxy-2′-fluoro-5-methyl-1-beta-d-arabinofuranosyluracil as a potential gene imaging agent for HSV-tk expression in vivo. Mol Imaging 2002;1 2:74–81CrossRefPubMedGoogle Scholar
  51. 51.
    Mangner TJ, Klecker RW, Anderson L, Shields AF. Synthesis of 2′-deoxy-2′-[18F]fluoro-beta-d-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. Nucl Med Biol 2003;30 3:215–24CrossRefPubMedGoogle Scholar
  52. 52.
    de Vries EF, van Dillen IJ, van Waarde A, Willemsen AT, Vaalburg W, Mulder NH, et al. Evaluation of [18F]FHPG as PET tracer for HSVtk gene expression. Nucl Med Biol 2003;30 6:651–60CrossRefPubMedGoogle Scholar
  53. 53.
    Min JJ, Iyer M, Gambhir SS. 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 2003;30 11:1547–60CrossRefPubMedGoogle Scholar
  54. 54.
    Alauddin MM, Shahinian A, Gordon EM, Conti PS. Evaluation of 2′-deoxy-2′-flouro-5-methyl-1-beta-d-arabinofuranosyluracil as a potential gene imaging agent for HSV-tk expression in vivo. Mol Imaging 2002;1 2:74–81CrossRefPubMedGoogle Scholar
  55. 55.
    Alauddin MM, Shahinian A, Park R, Tohme M, Fissekis JD, Conti PS. 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 12:2063–9PubMedGoogle Scholar
  56. 56.
    Alauddin MM, Shahinian A, Gordon EM, Conti PS. Direct comparison of radiolabeled probes FMAU, FHBG, and FHPG as PET imaging agents for HSV1-tk expression in a human breast cancer model. Mol Imaging 2004;3 2:76–84CrossRefPubMedGoogle Scholar
  57. 57.
    Alauddin MM, Shahinian A, Gordon EM, Conti PS. Direct comparison of radiolabeled probes FMAU, FHBG, and FHPG as PET imaging agents for HSV1-tk expression in a human breast cancer model. Mol Imaging 2004;3 2:76–84CrossRefPubMedGoogle Scholar
  58. 58.
    Deng WP, Yang WK, Lai WF, Liu RS, Hwang JJ, Yang DM, et al. Non-invasive in vivo imaging with radiolabelled FIAU for monitoring cancer gene therapy using herpes simplex virus type 1 thymidine kinase and ganciclovir. Eur J Nucl Med Mol Imaging 2004;31 1:99–109CrossRefPubMedGoogle Scholar
  59. 59.
    Alauddin MM, Shahinian A, Park R, Tohme M, Fissekis JD, Conti PS. Synthesis of 2′-deoxy-2′-[18F]fluoro-5-bromo-1-beta-d-arabinofuranosyluracil ([18F]-FBAU) and 2′-deoxy-2′-[18F]fluoro-5-chloro-1-beta-d-arabinofuranosyl-uracil ([18F]-FCAU), and their biological evaluation as markers for gene expression. Nucl Med Biol 2004;31 4:399–405CrossRefPubMedGoogle Scholar
  60. 60.
    MacLaren DC, Gambhir SS, Satyamurthy N, Barrio JR, Sharfstein S, Toyokuni T, et al. Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals. Gene Ther 1999;6:785–91CrossRefPubMedGoogle Scholar
  61. 61.
    Liang Q, Satyamurthy N, Barrio JR, Toyokuni T, Phelps MP, Gambhir SS, et al. 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 2001;8 19:1490–8CrossRefPubMedGoogle Scholar
  62. 62.
    Anderson CJ, Dehdashti F, Cutler PD, Schwarz SW, Laforest R, Bass LA, et al. 64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors. J Nucl Med 2001;42:213–21PubMedGoogle Scholar
  63. 63.
    Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, et al. PET imaging of somatostatin receptors using 68Ga-DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med 2001;42:1053–6PubMedGoogle Scholar
  64. 64.
    Zinn KR, Chaudhuri TR. The type 2 human somatostatin receptor as a platform for reporter gene imaging. Eur J Nucl Med 2002;29:388–99CrossRefGoogle Scholar
  65. 65.
    Wester HJ, Schottelius M, Scheidhauer K, Meisetschlager G, Herz M, Rau FC, et al. PET imaging of somatostatin receptors: design, synthesis and preclinical evaluation of a novel 18F-labelled, carbohydrated analogue of octreotide. Eur J Nucl Med Mol Imaging 2003;30 1:117–22CrossRefPubMedGoogle Scholar
  66. 66.
    Haberkorn U, Henze M, Altmann A, Jiang S, Morr I, Mahmut M, et al. Transfer of the human NaI symporter gene enhances iodide uptake in hepatoma cells. J Nucl Med 2001;42:317–25PubMedGoogle Scholar
  67. 67.
    Anton M, Wagner B, Haubner R, Bodenstein C, Essien BE, Bonisch H, et al. Use of the norepinephrine transporter as a reporter gene for non-invasive imaging of genetically modified cells. J Gene Med 2004;6 1:119–26CrossRefPubMedGoogle Scholar
  68. 68.
    Chung JK. Sodium iodide symporter: its role in nuclear medicine. J Nucl Med 2002;43:1188–200PubMedGoogle Scholar
  69. 69.
    Yaghoubi SS, Wu L, Liang Q, Toyokuni T, Barrio JR, Namavari M, et al. Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors. Gene Ther 2001;8:1072–89CrossRefPubMedGoogle Scholar
  70. 70.
    Yaghoubi S, Barrio JR, Dahlbom M, Iyer M, Namavari M, Satyamurthy N, et al. Human pharmacokinetic and dosimetry studies of [18F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. J Nucl Med 2001;42 8:1225–34PubMedGoogle Scholar
  71. 71.
    Jacobs A, Braunlich I, Graf R, Lercher M, Sakaki T, Voges J, et al. Quantitative kinetics of [124I]FIAU in cat and man. J Nucl Med 2001;42 3:467–75PubMedGoogle Scholar
  72. 72.
    Peñuelas I, Mazzolini G, Boán JF, Sangro B, Martí-Climent J, Ruiz J, et al. Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology 2005;128 7:1787–95CrossRefPubMedGoogle Scholar
  73. 73.
    Jacobs A, Voges J, Reszka R, Lercher M, Gossmann A, Kracht L, et al. Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 2001;358:727–9CrossRefPubMedGoogle Scholar
  74. 74.
    Gambhir SS, Bauer E, Black ME, Liang Q, Kokoris MS, Barrio JR, et al. 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 2000;97(6):2785–90CrossRefPubMedGoogle Scholar
  75. 75.
    Gambhir SS, Barrio JR, Phelps ME, Iyer M, Namavari M, Satyamurthy N, et al. Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. Proc Natl Acad Sci U S A 1999;96:2333–8CrossRefPubMedGoogle Scholar
  76. 76.
    Barrio JR. The molecular basis of disease. In: Phelps ME, editor. PET, molecular imaging and its biological applications. Berlin Heidelberg New York: Springer; 2004. p. 270–320Google Scholar
  77. 77.
    Yaghoubi SS, Wu L, Liang Q, Toyokuni T, Barrio JR, Namavari M, et al. Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors. Gene Ther 2001;8 14:1072–80CrossRefPubMedGoogle Scholar
  78. 78.
    Hackman T, Doubrovin M, Balatoni J, Beresten T, Ponomarev V, Beattie B, et al. Imaging gene expression of cytosine-deaminase-herpes virus thymidine kinase fusion gene (CD/TK) expression with [124I]FIAU and PET. Mol Imaging 2002;1:36–42CrossRefPubMedGoogle Scholar
  79. 79.
    Ray P, De A, Min JJ, Tsien RY, Gambhir SS. Imaging tri-fusion multimodality reporter gene expression in living subjects. Cancer Res 2004;64 4:1323–30PubMedGoogle Scholar
  80. 80.
    Ray P, Wu AM, Gambhir SS. Optical bioluminescence and positron emission tomography imaging of a novel fusion reporter gene in tumor xenografts of living mice. Cancer Res 2003;63 6:1160–5PubMedGoogle Scholar
  81. 81.
    Ponomarev V, Doubrovin M, Serganova I, Vider J, Shavrin A, Beresten T, et al. A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging. Eur J Nucl Med Mol Imaging 2004;31 5:740–51CrossRefPubMedGoogle Scholar
  82. 82.
    Chen IY, Wu JC, Min JJ, Sundaresan G, Lewis X, Liang Q, et al. Micro-positron emission tomography imaging of cardiac gene expression in rats using bicistronic adenoviral vector-mediated gene delivery. Circulation 2004;109 11:1415–20CrossRefPubMedGoogle Scholar
  83. 83.
    Liang Q, Gotts J, Satyamurthy N, Barrio J, Phelps ME, Gambhir SS, et al. Noninvasive, repetitive, quantitative measurement of gene expression from a bicistronic message by positron emission tomography, following gene transfer with adenovirus. Mol Ther 2002;6 1:73–82CrossRefPubMedGoogle Scholar
  84. 84.
    Yu Y, Annala AJ, Barrio JR, Toyokuni T, Satyamurthy N, Namavari M, et al. Quantification of target gene expression by imaging reporter gene expression in living animals. Nat Med 2000;6 8:933–7CrossRefPubMedGoogle Scholar
  85. 85.
    Sun X, Annala AJ, Yaghoubi SS, Barrio JR, Nguyen KN, Toyokuni T, et al. Quantitative imaging of gene induction in living animals. Gene Ther 2001;8 20:1572–9CrossRefPubMedGoogle Scholar
  86. 86.
    Ray S, Paulmurugan R, Hildebrandt I, Iyer M, Wu L, Carey M, et al. Novel bidirectional vector strategy for amplification of therapeutic and reporter gene expression. Hum Gene Ther 2004;15 7:681–90CrossRefPubMedGoogle Scholar
  87. 87.
    Hoekstra CJ, Paglianiti I, Hoekstra OS, Smit EF, Postmus PE, Teule GJ, et al. Monitoring response to therapy in cancer using [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography: an overview of different analytical methods. Eur J Nucl Med 2000;27:731–43CrossRefPubMedGoogle Scholar
  88. 88.
    Kitagawa Y, Sadato N, Azuma H ,Ogasawara T, Yoshida M, Ishii Y, et al. FDG PET to evaluate combined intra-arterial chemotherapy and radiotherapy of head and neck neoplasms. J Nucl Med 1999;40:1132–7PubMedGoogle Scholar
  89. 89.
    Denecke T, Rau B, Hoffmann KT, Hildebrandt B, Ruf J, Gutberlet M, et al. Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: is there a benefit in using functional imaging? Eur Radiol 2005;15 8:1658-66CrossRefPubMedGoogle Scholar
  90. 90.
    Tseng J, Dunnwald LK, Schubert EK, Link JM, Minoshima S, Muzi M, et al. 18F-FDG kinetics in locally advanced breast cancer: correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. J Nucl Med 2004;45 11:1829–37PubMedGoogle Scholar
  91. 91.
    Kumar R, Xiu Y, Potenta S, Mavi A, Zhuang H, Yu JQ, et al. 18F-FDG PET for evaluation of the treatment response in patients with gastrointestinal tract lymphomas. J Nucl Med 2004;45 11:1796–803PubMedGoogle Scholar
  92. 92.
    Avril NE, Weber WA. Monitoring response to treatment in patients utilizing PET. Radiol Clin North Am 2005;43 1:189–204CrossRefPubMedGoogle Scholar
  93. 93.
    Ishimori T, Saga T, Nagata Y, Nakamoto Y, Higashi T, Mamede M, et al. 18F-FDG and 11C-methionine PET for evaluation of treatment response of lung cancer after stereotactic radiotherapy. Ann Nucl Med 2004;18 8:669–74PubMedGoogle Scholar
  94. 94.
    Haberkorn U, Altmann A, Morr I, Germann C, Oberdorfer F, Van Kaick G. Multitracer studies during gene therapy of hepatoma cells with herpes simplex virus thymidine kinase and ganciclovir. J Nucl Med 1997;38:1048–54PubMedGoogle Scholar
  95. 95.
    Namba H, Iwadate Y, Iyo M, Fukushi K, Irie T, Sueyoshi K, et al. Glucose and methionine uptake by rat brain tumor treated with pro-drug activated gene therapy. Nucl Med Biol 1998;25:247–50CrossRefPubMedGoogle Scholar
  96. 96.
    Yaghoubi SS, Barrio JR, Namavari M, Satyamurthy N, Phelps ME, Herschman HR, et al. Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography. Cancer Gene Ther 2005;12 3:329–39CrossRefPubMedGoogle Scholar
  97. 97.
    Morin KW, Knaus EE, Wiebe LI, Xia H, McEwan AJ. Reporter gene imaging: effects of ganciclovir treatment on nucleoside uptake, hypoxia and perfusion in a murine gene therapy tumour model that expresses herpes simplex type-1 thymidine kinase. Nucl Med Commun 2000;21:129–37CrossRefPubMedGoogle Scholar
  98. 98.
    Haberkorn U, Bellemann ME, Gerlach L, Morr I, Trojan H, Brix G, et al. Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase. Gene Ther 1998;5:880–7CrossRefPubMedGoogle Scholar
  99. 99.
    Haberkorn U, Altmann A, Kamencic H, Morr I, Traut U, Henze M, et al. Glucose transport and apoptosis after gene therapy with HSV thymidine kinase. Eur J Nucl Med 2001;28:1690–6CrossRefPubMedGoogle Scholar
  100. 100.
    Schmidt KS, Hoffend JS, Altmann A, Strauss LG, Dimitrakopoulou-Strauss A, Engelhardt B, et al. Transfer of the sFLT-1 gene in Morris hepatoma results in decreased growth and perfusion and induction of genes associated with stress response. Clin Cancer Res 2005;11:2132–40PubMedGoogle Scholar
  101. 101.
    Bankiewicz KS, Eberling JL, Kohutnicka M, Jagust W, Pivirotto P, Bringas J, et al. Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol 2000;164:2–14CrossRefPubMedGoogle Scholar
  102. 102.
    World Health Organization. Handbook of reporting results of cancer treatment, vol. 48. Geneva, Switzerland: WHO; 1979Google Scholar
  103. 103.
    Gambhir SS, Barrio JR, Wu L, Iyer M, Namavari M, Satyamurthy N, et al. Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir. J Nucl Med 1998;39:2003–11PubMedGoogle Scholar
  104. 104.
    MacLaren DC, Gambhir SS, Satyamurthy N, Barrio JR, Sharfstein S, Toyokuni T, et al. Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals. Gene Ther 1999;6:785–91CrossRefPubMedGoogle Scholar
  105. 105.
    Doubrovin M, Ponomarev V, Beresten T, Balatoni J, Bornmann W, Finn R, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci U S A 2001;98:9300–5CrossRefPubMedGoogle Scholar
  106. 106.
    Min JJ, Gambhir SS. Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects. Gene Ther 2004;11:115–25PubMedGoogle Scholar
  107. 107.
    Green LA, Yap C, Nguyen K, Barrio JR, Namavari M, Satyamurthy N, et al. Indirect monitoring of endogenous gene expression by PET imaging of reporter gene expression in transgenic mice. Mol Imaging Biol 2002;4:71–81CrossRefPubMedGoogle Scholar
  108. 108.
    Wu JC, Chen IY, Wang Y, Tseng J, Salek M, Chhabra A, et al. Molecular imaging of the kinetics of VEGF gene expression in ischemic myocardium. Circulation 2004;110:685–91CrossRefPubMedGoogle Scholar
  109. 109.
    De A, Lewis X, Gambhir SS. Noninvasive imaging of lentiviral-mediated reporter gene expression in living mice. Molec Ther 2003;7:681–91CrossRefGoogle Scholar
  110. 110.
    Green LA, Nguyen K, Berenji B, Bauer E, Barrio JR, Namavari M, et al. A tracer kinetic model for FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using positron emission tomography. J Nucl Med 2004;45:1560–70PubMedGoogle Scholar
  111. 111.
    Kang KW, Min J, Chen X, Gambhir SS. Comparison of [14C]FMAU, [3H]FEAU, [14C]FIAU and [3H]PCV for imaging wild type and mutant herpes simplex virus type 1 thymidine kinase reporter gene expression in cell culture. Mol Imaging Biol 2005. DOI: 10.1007/s11307-005-0010-7Google Scholar
  112. 112.
    Marshall E. Gene therapy death prompts review of adenovirus vector. Science 1999;286:2244–5CrossRefPubMedGoogle Scholar
  113. 113.
    Romano G. Systems for regulated or tissue-specific gene expression. Drug News Perspect 2004;17 2:85–90CrossRefPubMedGoogle Scholar
  114. 114.
    Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2003;348 3:255–6CrossRefPubMedGoogle Scholar
  115. 115.
    Kaiser J. Seeking the cause of induced leukemias in X-SCID trial. Science 2003;299:457–608Google Scholar
  116. 116.
    Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genetics 2003;4:346–58CrossRefGoogle Scholar
  117. 117.
    Schellingerhout D, Bogdanov A Jr, Marecos E, Spear M, Breakefield X, Weissleder R. Mapping the in vivo distribution of herpes simplex virions. Hum Gene Ther 1998;9:1543–9PubMedGoogle Scholar
  118. 118.
    Zinn KR, Douglas JT, Smyth CA, Liu HG, Wu Q, Krasnykh VN, et al. Imaging and tissue biodistribution of 99mTc-labeled adenovirus knob (serotype 5). Gene Ther 1998;5:798–808CrossRefPubMedGoogle Scholar
  119. 119.
    Lerondel S, Le Pape A, Sene C, Faure L, Bernard S, Diot P, et al. Radioisotopic imaging allows optimization of adenovirus lung deposition for cystic fibrosis gene therapy. Hum Gene Ther 2001;12 1:1–11CrossRefPubMedGoogle Scholar
  120. 120.
    Tannous BA, Kim D, Fernandez JL, Weissleder R, Breakefield XO. Codon optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Molec Ther 2005;11 3:435–43CrossRefGoogle Scholar
  121. 121.
    Toso C, Zaidi H, Morel P, Armanet M, Andres A, Pernin N, et al. Positron-emission tomography imaging of early events after transplantation of islets of Langerhans. Transplantation 2005;79 3:353–5CrossRefPubMedGoogle Scholar
  122. 122.
    Adonai N, Nguyen KN, Walsh J, Iyer M, Toyokuni T, Phelps ME, et al. 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 2002;99 5:3030–5CrossRefPubMedGoogle Scholar
  123. 123.
    Tamura M, Unno K, Yonezawa S, Hattori K, Nakashima E, Tsukada H, et al. In vivo trafficking of endothelial progenitor cells their possible involvement in the tumor neovascularization. Life Sci 2004;75 5:575–84CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Nuclear Medicine, University HospitalUniversity of NavarraPamplonaSpain
  2. 2.Department of Nuclear MedicineUniversity of HeidelbergHeidelbergGermany
  3. 3.Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X ProgramStanford UniversityStanfordUSA
  4. 4.Department of BioengineeringStanford UniversityStanfordUSA

Personalised recommendations