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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-12-2005 | Supplement

Gene therapy imaging in patients for oncological applications

Authors: Iván Peñuelas, Uwe Haberkorn, Shahriar Yaghoubi, Sanjiv S. Gambhir

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Special Issue 2/2005

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.

International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 2001;409:860–921

Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science 2001;291:1304–51CrossRefPubMed

Pfeifer A, Verma IM. Gene therapy: promises and problems. Annu Rev Genomics Hum Genet 2001;2:177–211CrossRefPubMed

Verma I, Somia N. Gene therapy—promises, problems and prospects. Nature 1997;389:239–42CrossRefPubMed

Mulligan RC. The basic science of gene therapy. Science 1993;260:926–93PubMed

http://www.wiley.co.uk/genetherapy/clinical/

Edelstein ML, Abedi MR, Wixon J, Edelstein RMJ. Gene therapy clinical trials worldwide 1989–2004—an overview. Gene Med 2004;6:597–602CrossRef

El-Aneed A. An overview of current delivery systems in cancer gene therapy. J Control Release 2004;94 1:1–14CrossRefPubMed

Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med 2001;7:33–40CrossRefPubMed

10.

Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genetics 2003;4:346–58CrossRef

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;6:225–38CrossRefPubMed

12.

Nichol C, Kim EE. Molecular imaging and gene therapy. J Nucl Med 2001;42:1368–74PubMed

13.

Larson SM, Tjuvajev J, Blasberg R. Triumph over mischance: a role for nuclear medicine in gene therapy. J Nucl Med 1997;38:1230–3PubMed

14.

Haberkorn U, Mier W, Eisenhut M. Scintigraphic imaging of gene expression and gene transfer. Curr Med Chem 2005;12 7:779–94CrossRefPubMed

15.

Bogdanov A, Weissleder R. In vivo imaging of gene delivery and expression. Trends Biotech 2002;20 8:S11–8CrossRef

16.

Vogt Sionov RV, Haupt Y. The cellular response to p53: the decision between life and death. Oncogene 1999;18:6145–57CrossRefPubMed

17.

Zeimet AG, Marth C. Why did p53 gene therapy fail in ovarian cancer? Lancet Oncol 2003;4 7:415–22CrossRefPubMed

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 1:17–26CrossRefPubMed

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;82:1023–8PubMed

20.

Crooke ST. Antisense strategies. Curr Mol Med 2004;4 5:465–87

21.

Bi F, Liu N, Fan D. Small interfering RNA: a new tool for gene therapy. Curr Gene Ther 2003;3 5:411–7CrossRefPubMed

22.

Bagheri S, Kashani-Sabet M. Ribozymes in the age of molecular therapeutics. Curr Mol Med 2004;4 5:489–506CrossRefPubMed

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 1:13–26PubMed

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 21:5274–83PubMed

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 3:307–22PubMed

26.

Ribas A, Butterfield LH, Economou JS. Genetic immunotherapy for cancer. Oncologist 2000;5 2:87–98CrossRefPubMed

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 8:1389–97CrossRefPubMed

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 5:999–1010CrossRefPubMed

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 4:346–55CrossRefPubMed

30.

Isayeva T, Kumar S, Ponnazhagan S. Anti-angiogenic gene therapy for cancer (review). Int J Oncol 2004;25 2:335–43PubMed

31.

Ntziachristos V, Bremer C, Graves EE, Ripoll J, Weissleder R. In vivo tomographic imaging of near-infrared fluorescent probes. Mol Imaging 2002;1 2:82–8CrossRefPubMed

32.

Ntziachristos V, Tung CH, Bremer C, Weissleder R. Fluorescence molecular tomography resolves protease activity in vivo. Nat Med 2002;8 7:757–60CrossRefPubMed

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 3:351–5CrossRefPubMed

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 4:450–4CrossRefPubMed

35.

Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2002;2:683–93CrossRefPubMed

36.

Phelps ME. PET: molecular imaging and its biological applications. Berlin Heidelberg New York: Springer; 2004

37.

Chatziioannou AF. PET scanners dedicated to molecular imaging of small animal models. Mol Imaging Biol 2002;4 1:47–63CrossRefPubMed

38.

Phelps ME. Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci U S A 2000;97 16:9226–33CrossRefPubMed

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;6:933–7CrossRefPubMed

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;4:27–33CrossRefPubMed

41.

Haberkorn U, Altmann A, Mier W, Eisenhut M. Impact of functional genomics and proteomics on radionuclide imaging. Semin Nucl Med 2004;34 1:4–22CrossRef

42.

Gambhir SS, Barrio JR, Herschman HR, Phelps ME. Assays for noninvasive imaging of reporter gene expression. Nucl Med Biol 1999;26 5:481–90CrossRefPubMed

43.

Gambhir SS, Barrio JR, Herschman HR, Phelps ME. Imaging gene expression: principles and assays. J Nucl Cardiol 1999;6 2:219–33

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;37:87–94PubMed

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;38:287–94PubMed

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 6:721–9CrossRefPubMed

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 3:467–75PubMed

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 7:939–47CrossRefPubMed

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 8:1072–83PubMed

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 2:74–81CrossRefPubMed

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 3:215–24CrossRefPubMed

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 6:651–60CrossRefPubMed

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 11:1547–60CrossRefPubMed

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 2:74–81CrossRefPubMed

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 12:2063–9PubMed

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 2:76–84CrossRefPubMed

57.

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 1:99–109CrossRefPubMed

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 4:399–405CrossRefPubMed

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;6:785–91CrossRefPubMed

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 19:1490–8CrossRefPubMed

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;42:213–21PubMed

63.

Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, et al. PET imaging of somatostatin receptors using⁶⁸Ga-DOTA-D-Phe¹-Tyr³-octreotide: first results in patients with meningiomas. J Nucl Med 2001;42:1053–6PubMed

64.

Zinn KR, Chaudhuri TR. The type 2 human somatostatin receptor as a platform for reporter gene imaging. Eur J Nucl Med 2002;29:388–99CrossRef

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 novel¹⁸F-labelled, carbohydrated analogue of octreotide. Eur J Nucl Med Mol Imaging 2003;30 1:117–22CrossRefPubMed

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;42:317–25PubMed

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 1:119–26CrossRefPubMed

68.

Chung JK. Sodium iodide symporter: its role in nuclear medicine. J Nucl Med 2002;43:1188–200PubMed

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;8:1072–89CrossRefPubMed

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 8:1225–34PubMed

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 3:467–75PubMed

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 7:1787–95CrossRefPubMed

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;358:727–9CrossRefPubMed

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):2785–90CrossRefPubMed

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;96:2333–8CrossRefPubMed

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. 270–320

77.

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;1:36–42CrossRefPubMed

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 4:1323–30PubMed

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 6:1160–5PubMed

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 5:740–51CrossRefPubMed

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 11:1415–20CrossRefPubMed

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 1:73–82CrossRefPubMed

84.

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 20:1572–9CrossRefPubMed

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 7:681–90CrossRefPubMed

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;27:731–43CrossRefPubMed

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;40:1132–7PubMed

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 8:1658-66CrossRefPubMed

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 11:1829–37PubMed

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 11:1796–803PubMed

92.

Avril NE, Weber WA. Monitoring response to treatment in patients utilizing PET. Radiol Clin North Am 2005;43 1:189–204CrossRefPubMed

93.

Ishimori T, Saga T, Nagata Y, Nakamoto Y, Higashi T, Mamede M, et al.¹⁸F-FDG and¹¹C-methionine PET for evaluation of treatment response of lung cancer after stereotactic radiotherapy. Ann Nucl Med 2004;18 8:669–74PubMed

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;38:1048–54PubMed

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;25:247–50CrossRefPubMed

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 3:329–39CrossRefPubMed

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;21:129–37CrossRefPubMed

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;5:880–7CrossRefPubMed

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;28:1690–6CrossRefPubMed

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;11:2132–40PubMed

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;164:2–14CrossRefPubMed

102.

World Health Organization. Handbook of reporting results of cancer treatment, vol. 48. Geneva, Switzerland: WHO; 1979

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;39:2003–11PubMed

104.

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;98:9300–5CrossRefPubMed

106.

Min JJ, Gambhir SS. Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects. Gene Ther 2004;11:115–25PubMed

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;4:71–81CrossRefPubMed

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;110:685–91CrossRefPubMed

109.

De A, Lewis X, Gambhir SS. Noninvasive imaging of lentiviral-mediated reporter gene expression in living mice. Molec Ther 2003;7:681–91CrossRef

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;45:1560–70PubMed

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/s11307-005-0010-7

112.

Marshall E. Gene therapy death prompts review of adenovirus vector. Science 1999;286:2244–5CrossRefPubMed

113.

Romano G. Systems for regulated or tissue-specific gene expression. Drug News Perspect 2004;17 2:85–90CrossRefPubMed

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 3:255–6CrossRefPubMed

115.

Kaiser J. Seeking the cause of induced leukemias in X-SCID trial. Science 2003;299:457–608

116.

Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genetics 2003;4:346–58CrossRef

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;9:1543–9PubMed

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;5:798–808CrossRefPubMed

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 1:1–11CrossRefPubMed

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 3:435–43CrossRef

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 3:353–5CrossRefPubMed

122.

Adonai N, Nguyen KN, Walsh J, Iyer M, Toyokuni T, Phelps ME, et al. Ex vivo cell labeling with⁶⁴Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc Natl Acad Sci U S A 2002;99 5:3030–5CrossRefPubMed

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 5:575–84CrossRefPubMed

Title: Gene therapy imaging in patients for oncological applications
Authors: Iván Peñuelas
Uwe Haberkorn
Shahriar Yaghoubi
Sanjiv S. Gambhir
Publication date: 01-12-2005
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue Special Issue 2/2005
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-005-1928-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Gene therapy imaging in patients for oncological applications

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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