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Defining the success of cardiac gene therapy: how can nuclear imaging contribute?

  • Molecular Imaging
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Gene therapy is a promising modality for the treatment of various cardiovascular diseases such as ischaemia, heart failure, restenosis after revascularisation, hypertension and hyperlipidaemia. An increasing number of approaches are moving from experimental and preclinical validation to clinical application, and several multi-centre trials are currently underway. Despite the rapid progress in cardiac gene therapy, many basic tools and principles remain under development. Questions with regard to the optimal method for gene delivery in a given situation remain open, as do questions concerning therapeutic efficacy and the time course and magnitude of gene expression in target and remote areas. Nuclear imaging provides valuable tools to address these open issues non-invasively. Functional effects of molecular therapy at the tissue level can be identified using tracers of blood flow, metabolism, innervation or cell death. The use of reporter genes and radiolabelled reporter probes allows for non-invasive assessment of location, magnitude and persistence of transgene expression in the heart and the whole body. Co-expression of a reporter gene will allow for indirect imaging of the expression of a therapeutic gene of choice, and linkage of measures of transgene expression to downstream functional effects will enhance the understanding of basic mechanisms of cardiac gene therapy. Hence, nuclear imaging offers great potential to facilitate and refine the determination of therapeutic effects in preclinical and clinical cardiovascular gene therapy.

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References

  1. Isner JM. Myocardial gene therapy. Nature 2002; 415:234–239.

    Google Scholar 

  2. Nabel EG. Gene therapy for cardiovascular disease. Circulation 1995; 91:541–548.

    Google Scholar 

  3. Welsh S, Kay SA. Reporter gene expression for monitoring gene transfer. Curr Opin Biotechnol 1997; 8:617–622.

    Google Scholar 

  4. Buchholz CJ, Stitz J, Cichutek K. Retroviral cell targeting vectors. Curr Opin Mol Ther 1999; 1:613–621.

    Google Scholar 

  5. Lusky M, Christ M, Rittner K, et al. In vitro and in vivo biology of recombinant adenovirus vectors with E1, E1/E2A, or E1/E4 deleted. J Virol 1998; 72:2022–2032.

    Google Scholar 

  6. Fisher KJ, Jooss K, Alston J, et al. Recombinant adeno-associated virus for muscle directed gene therapy. Nat Med 1997; 3:306–312.

    Google Scholar 

  7. Wolff JA, Ludtke JJ, Acsadi G, et al. Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum Mol Genet 1992; 1:363–369.

    Google Scholar 

  8. Nabel EG, Plautz G, Nabel GJ. Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science 1990; 249:1285–1288.

    Google Scholar 

  9. Binley K, Iqball S, Kingsman A, et al. An adenoviral vector regulated by hypoxia for the treatment of ischaemic disease and cancer. Gene Ther 1999; 6:1721–1727.

    Google Scholar 

  10. De Geest B, Van Linthout S, Lox M, et al. Sustained expression of human apolipoprotein A-I after adenoviral gene transfer in C57BL/6 mice: role of apolipoprotein A-I promoter, apolipoprotein A-I introns, and human apolipoprotein E enhancer. Hum Gene Ther 2000; 11:101–112.

    Google Scholar 

  11. Guzman RJ, Lemarchand P, Crystal RG, et al. Efficient gene transfer into myocardium by direct injection of adenovirus vectors. Circ Res 1993; 73:1202–1207.

    Google Scholar 

  12. Barr E, Carroll J, Kalynych AM, et al. Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus. Gene Ther 1994; 1:51–58.

    Google Scholar 

  13. Boekstegers P, von Degenfeld G, Giehrl W, et al. Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins. Gene Ther 2000; 7:232–240.

    Google Scholar 

  14. Fromes Y, Salmon A, Wang X, et al. Gene delivery to the myocardium by intrapericardial injection. Gene Ther 1999; 6:683–688.

    Google Scholar 

  15. Hajjar RJ, Schmidt U, Matsui T, et al. Modulation of ventricular function through gene transfer in vivo. Proc Natl Acad Sci U S A 1998; 95:5251–5256.

    Google Scholar 

  16. Maurice JP, Hata JA, Shah AS, et al. Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-adrenergic receptor gene delivery. J Clin Invest 1999; 104:21–29.

    Google Scholar 

  17. Donahue JK, Kikkawa K, Johns DC, et al. Ultrarapid, highly efficient viral gene transfer to the heart. Proc Natl Acad Sci U S A 1997; 94:4664–4668.

    Google Scholar 

  18. Marshall DJ, Palasis M, Lepore JJ, et al. Biocompatibility of cardiovascular gene delivery catheters with adenovirus vectors: an important determinant of the efficiency of cardiovascular gene transfer. Mol Ther 2000; 1:423–429.

    Google Scholar 

  19. Schumacher B, Hannekum A, Pecher P. Neoangiogenesis by local gene therapy: a new therapeutic concept in the treatment of coronary disease. Z Kardiol 2000; 7:23–30.

    Google Scholar 

  20. Takeshita S, Weir L, Chen D, et al. Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 1996; 227:628–635.

    Google Scholar 

  21. Takeshita S, Tsurumi Y, Couffinahl T, et al. Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. Lab Invest 1996; 75:487–501.

    Google Scholar 

  22. Mack CA, Patel SR, Schwarz EA, et al. Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. J Thorac Cardiovasc Surg 1998; 115:168–176; discussion 176–177.

    Google Scholar 

  23. Tio RA, Tkebuchava T, Scheuermann TH, et al. Intramyocardial gene therapy with naked DNA encoding vascular endothelial growth factor improves collateral flow to ischemic myocardium. Hum Gene Ther 1999; 10:2953–2960.

    Google Scholar 

  24. Vincent KA, Shyu KG, Luo Y, et al. Angiogenesis is induced in a rabbit model of hindlimb ischemia by naked DNA encoding an HIF-1alpha/VP16 hybrid transcription factor. Circulation 2000; 102:2255–2261.

    Google Scholar 

  25. Losordo DW, Vale PR, Symes JF, et al. Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 1998; 98:2800–2804.

    Google Scholar 

  26. Rosengart TK, Lee LY, Patel SR, et al. Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation 1999; 100:468–474.

    Google Scholar 

  27. Yoshida T, Watanabe M, Engelman DT, et al. Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial ischemia reperfusion injury. J Mol Cell Cardiol 1996; 28:1759–1767.

    Google Scholar 

  28. Yoshida T, Maulik N, Engelman RM, et al. Glutathione peroxidase knockout mice are susceptible to myocardial ischemia reperfusion injury. Circulation 1997; 96:II-216–II-220.

    Google Scholar 

  29. Jayakumar J, Suzuki K, Khan M, et al. Gene therapy for myocardial protection: transfection of donor hearts with heat shock protein 70 gene protects cardiac function against ischemia-reperfusion injury. Circulation 2000; 102:III302–III306.

    Google Scholar 

  30. Hajjar RJ, Kang JX, Gwathmey JK, et al. Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum calcium ATPase in isolated rat myocytes. Circulation 1997; 95:423–429.

    Google Scholar 

  31. Steg PG, Tahlil O, Aubailly N, et al. Reduction of restenosis after angioplasty in an atheromatous rabbit model by suicide gene therapy. Circulation 1997; 96:408–411.

    Google Scholar 

  32. Smith RC, Wills KN, Antelman D, et al. Adenoviral constructs encoding phosphorylation-competent full-length and truncated forms of the human retinoblastoma protein inhibit myocyte proliferation and neointima formation. Circulation 1997; 96:1899–1905.

    Google Scholar 

  33. Luo Z, Sata M, Nguyen T, et al. Adenovirus-mediated delivery of fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals. Circulation 1999; 99:1776–1779.

    Google Scholar 

  34. Van Belle E, Maillard L, Tio FO, et al. Accelerated endothelialization by local delivery of recombinant human vascular endothelial growth factor reduces in-stent intimal formation. Biochem Biophys Res Commun 1997; 235:311–316.

    Google Scholar 

  35. von der Leyen HE, Gibbons GH, Morishita R, et al. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci U S A 1995; 92:1137–1141.

    Google Scholar 

  36. Mann MJ, Gibbons GH, Hutchinson H, et al. Pressure-mediated oligonucleotide transfection of rat and human cardiovascular tissues. Proc Natl Acad Sci U S A 1999; 96:6411–6416.

    Google Scholar 

  37. Mann MJ, Whittemore AD, Donaldson MC, et al. Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial. Lancet 1999; 354:1493–1498.

    Google Scholar 

  38. del Monte F, Harding SE, Schmidt U, et al. Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a. Circulation 1999; 100:2308–2311.

    Google Scholar 

  39. Miyamoto MI, del Monte F, Schmidt U, et al. Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc Natl Acad Sci U S A 2000; 97:793–798.

    Google Scholar 

  40. He H, Meyer M, Martin JL, et al. Effects of mutant and antisense RNA of phospholamban on SR Ca(2+)-ATPase activity and cardiac myocyte contractility. Circulation 1999; 100:974–980.

    Google Scholar 

  41. Akhter SA, Skaer CA, Kypson AP, et al. Restoration of beta-adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer. Proc Natl Acad Sci U S A 1997; 94:12100–12105.

    Google Scholar 

  42. Shah AS, Lilly RE, Kypson AP, et al. Intracoronary adenovirus-mediated delivery and overexpression of the beta(2)-adrenergic receptor in the heart: prospects for molecular ventricular assistance. Circulation 2000; 101:408–414.

    Google Scholar 

  43. Weig HJ, Laugwitz KL, Moretti A, et al. Enhanced cardiac contractility after gene transfer of V2 vasopressin receptors in vivo by ultrasound-guided injection or transcoronary delivery. Circulation 2000; 101:1578–1585.

    Google Scholar 

  44. Hirota H, Chen J, Betz UA, et al. Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 1999; 97:189–198.

    Google Scholar 

  45. Kirshenbaum LA, de Moissac D. The bcl-2 gene product prevents programmed cell death of ventricular myocytes. Circulation 1997; 96:1580–1585.

    Google Scholar 

  46. Laugwitz KL, Moretti A, Weig HJ, et al. Blocking caspase-activated apoptosis improves contractility in failing myocardium. Hum Gene Ther 2001; 12:2051–2063.

    Google Scholar 

  47. Buerke M, Murohara T, Skurk C, et al. Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. Proc Natl Acad Sci U S A 1995; 92:8031–8035.

    Google Scholar 

  48. Ardehali A, Reddy R, Laks H. Gene therapy and heart transplantation. Expert Opin Investig Drugs 2000; 9:1021–1027.

    Google Scholar 

  49. Lee J, Laks H, Drinkwater DC, et al. Cardiac gene transfer by intracoronary infusion of adenovirus vector-mediated reporter gene in the transplanted mouse heart. J Thorac Cardiovasc Surg 1996; 111:246–252.

    Google Scholar 

  50. Iwata A, Sai S, Nitta Y, et al. Liposome-mediated gene transfection of endothelial nitric oxide synthase reduces endothelial activation and leukocyte infiltration in transplanted hearts. Circulation 2001; 103:2753–2759.

    Google Scholar 

  51. Guillot C, Guillonneau C, Mathieu P, et al. Prolonged blockade of CD40-CD40 ligand interactions by gene transfer of CD40Ig results in long-term heart allograft survival and donor-specific hyporesponsiveness, but does not prevent chronic rejection. J Immunol 2002; 168:1600–1609.

    Google Scholar 

  52. Chen SJ, Rader DJ, Tazelaar J, et al. Prolonged correction of hyperlipidemia in mice with familial hypercholesterolemia using an adeno-associated viral vector expressing very-low-density lipoprotein receptor. Mol Ther 2000; 2:256–261.

    Google Scholar 

  53. Kozarsky KF, Donahee MH, Glick JM, et al. Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 2000; 20:721–727.

    Google Scholar 

  54. Tangirala RK, Tsukamoto K, Chun SH, et al. Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice. Circulation 1999; 100:1816–1822.

    Google Scholar 

  55. Chao J, Zhang JJ, Lin KF, et al. Human kallikrein gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive rats. Hum Gene Ther 1998; 9:21–31.

    Google Scholar 

  56. Dobrzynski E, Wang C, Chao J, et al. Adrenomedullin gene delivery attenuates hypertension, cardiac remodeling, and renal injury in deoxycorticosterone acetate-salt hypertensive rats. Hypertension 2000; 36:995–1001.

    Google Scholar 

  57. Lin KF, Chao L, Chao J. Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery. Hypertension 1997; 30:307–313.

    Google Scholar 

  58. Martens JR, Reaves PY, Lu D, et al. Prevention of renovascular and cardiac pathophysiological changes in hypertension by angiotensin II type 1 receptor antisense gene therapy. Proc Natl Acad Sci U S A 1998; 95:2664–2669.

    Google Scholar 

  59. Bengel FM, Schwaiger M. Nuclear medicine studies of the heart. Eur Radiol 1998; 8:1698–1706.

    Google Scholar 

  60. Vale PR, Losordo DW, Milliken CE, et al. Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia. Circulation 2001; 103:2138–2143.

    Google Scholar 

  61. Losordo DW, Vale PR, Hendel RC, et al. Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia. Circulation 2002; 105:2012–2018.

    Google Scholar 

  62. Henry TD, Annex BH, Azrin MA, et al. Final results of the VIVA trial of rhVEGF for human therapeutic angiogenesis [abstract]. Circulation 1999; 100 (Suppl I):I-476.

    Google Scholar 

  63. Simons M, Annex BH, Laham RJ, et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial. Circulation 2002; 105:788–793.

    Google Scholar 

  64. Bengel FM, Permanetter B, Ungerer M, et al. Non-invasive estimation of myocardial efficiency using positron emission tomography and carbon-11 acetate—comparison between the normal and failing human heart. Eur J Nucl Med 2000; 27:319–326.

    Google Scholar 

  65. Beanlands RS, Nahmias C, Gordon E, et al. The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: a double-blind, placebo-controlled, positron-emission tomography study. Circulation 2000; 102:2070–2075.

    Google Scholar 

  66. Merlet P, Delforge J, Syrota A, et al. Positron emission tomography with11C CGP-12177 to assess beta-adrenergic receptor concentration in idiopathic dilated cardiomyopathy. Circulation 1993; 87:1169–1178.

    Google Scholar 

  67. Ungerer M, Hartmann F, Karoglan M, et al. Regional in vivo and in vitro characterization of autonomic innervation in cardiomyopathic human heart. Circulation 1998; 97:174–180.

    Google Scholar 

  68. Schafers M, Dutka D, Rhodes CG, et al. Myocardial presynaptic and postsynaptic autonomic dysfunction in hypertrophic cardiomyopathy. Circ Res 1998; 82:57–62.

    Google Scholar 

  69. Blankenberg F, Narula J, Strauss HW. In vivo detection of apoptotic cell death: a necessary measurement for evaluating therapy for myocarditis, ischemia, and heart failure. J Nucl Cardiol 1999; 6:531–539.

    Google Scholar 

  70. Narula J, Petrov A, Bianchi C, et al. Noninvasive localization of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 F(ab')2 specific for the proliferating smooth muscle cells of human atheroma. Imaging with conventional and negative charge-modified antibody fragments. Circulation 1995; 92:474–484.

    Google Scholar 

  71. Ohtsuki K, Hayase M, Akashi K, et al. Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: an autoradiographic study. Circulation 2001; 104:203–208.

    Google Scholar 

  72. Zinn KR, Douglas JT, Smyth CA, et al. Imaging and tissue biodistribution of99mTc-labeled adenovirus knob (serotype 5). Gene Ther 1998; 5:798–808.

    Google Scholar 

  73. Harrington KJ, Rowlinson-Busza G, Syrigos KN, et al. Biodistribution and pharmacokinetics of111In-DTPA-labelled pegylated liposomes in a human tumour xenograft model: implications for novel targeting strategies. Br J Cancer 2000; 83:232–238.

    Google Scholar 

  74. Fukumura D, Xavier R, Sugiura T, et al. Tumor induction of VEGF promoter activity in stromal cells. Cell 1998; 94:715–725.

    Google Scholar 

  75. Sweeney TJ, Mailander V, Tucker AA, et al. Visualizing the kinetics of tumor-cell clearance in living animals. Proc Natl Acad Sci U S A 1999; 96:12044–12049.

    Google Scholar 

  76. Weissleder R, Tung CH, Mahmood U, et al. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999; 17:375–378.

    Google Scholar 

  77. Hogemann D, Josephson L, Weissleder R, et al. Improvement of MRI probes to allow efficient detection of gene expression. Bioconjug Chem. 2000; 11:941–946.

    Google Scholar 

  78. Louie AY, Huber MM, Ahrens ET, et al. In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 2000; 18:321–325.

    Google Scholar 

  79. Stegman LD, Rehemtulla A, Beattie B, et al. Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy. Proc Natl Acad Sci U S A 1999; 96:9821–9826.

    Google Scholar 

  80. Freeman SM, Whartenby KA, Freeman JL, et al. In situ use of suicide genes for cancer therapy. Semin Oncol 1996; 23:31–45.

    Google Scholar 

  81. Saito Y, Rubenstein R, Price RW, et al. Diagnostic imaging of herpes simplex virus encephalitis using a radiolabeled antiviral drug: autoradiographic assessment in an animal model. Ann Neurol 1984; 15:548–558.

    Google Scholar 

  82. Gambhir SS, Herschman HR, Cherry SR, et al. Imaging transgene expression with radionuclide imaging technologies. Neoplasia 2000; 2:118–138.

    Google Scholar 

  83. Tjuvajev JG, Stockhammer G, Desai R, et al. Imaging the expression of transfected genes in vivo. Cancer Res 1995; 55:6126–6132.

    Google Scholar 

  84. Tjuvajev JG, Finn R, Watanabe K, et al. Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy. Cancer Res 1996; 56:4087–4095.

    Google Scholar 

  85. Tjuvajev JG, Avril N, Oku T, et al. Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. Cancer Res 1998; 58:4333–4341.

    Google Scholar 

  86. Tjuvajev JG, Chen SH, Joshi A, et al. Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo. Cancer Res 1999; 59:5186–5193.

    Google Scholar 

  87. Haubner R, Avril N, Hantzopoulos PA, et al. In vivo imaging of herpes simplex virus type 1 thymidine kinase gene expression: early kinetics of radiolabelled FIAU. Eur J Nucl Med 2000; 27:283–291.

    Google Scholar 

  88. Alauddin MM, Conti PS, Mazza SM, et al. 9-[(3-[18F]-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]-FHPG): a potential imaging agent of viral infection and gene therapy using PET. Nucl Med Biol 1996; 23:787–792.

    Google Scholar 

  89. Alauddin MM, Conti PS. 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 1998; 25:175–180.

    Google Scholar 

  90. Gambhir SS, Barrio JR, Wu L, 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; 39:2003–2011.

    Google Scholar 

  91. Brust P, Haubner R, Friedrich A, 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; 28:721–729.

    Google Scholar 

  92. Gambhir SS, Bauer E, Black ME, 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; 97:2785–2790.

    Google Scholar 

  93. Iyer M, Wu L, Carey M, et al. Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters. Proc Natl Acad Sci U S A 2001; 98:14595–14600.

    Google Scholar 

  94. Doubrovin M, Ponomarev V, Beresten T, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci U S A 2001; 98:9300–9305.

    Google Scholar 

  95. Jacobs A, Voges J, Reszka R, et al. Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 2001; 358:727–729.

    Google Scholar 

  96. MacLaren DC, Gambhir SS, Satyamurthy N, et al. Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals. Gene Ther 1999; 6:785–791.

    Google Scholar 

  97. Zinn KR, Buchsbaum DJ, Chaudhuri TR, et al. Noninvasive monitoring of gene transfer using a reporter receptor imaged with a high-affinity peptide radiolabeled with99mTc or 188Re. J Nucl Med 2000; 41:887–895.

    Google Scholar 

  98. Mandell RB, Mandell LZ, Link CJ Jr. Radioisotope concentrator gene therapy using the sodium/iodide symporter gene. Cancer Res 1999; 59:661–668.

    Google Scholar 

  99. Bengel FM, Anton M, Avril N, et al. Uptake of radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-d-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase gene: the cellular basis for cardiac gene imaging. Circulation 2000; 102:948–950.

    Google Scholar 

  100. Wu JC, Inubushi M, Sundaresan G, et al. Optical imaging of cardiac reporter gene expression in living rats. Circulation 2002; 105:1631–1634.

    Google Scholar 

  101. Wu JC, Inubushi M, Sundaresan G, et al. Positron emission tomography imaging of cardiac reporter gene expression in living rats. Circulation 2002; 106:180–183.

    Google Scholar 

  102. Inubushi M, Wu J, Gambhir SS, et al. PET reporter gene expression imaging in rat myocardium. Circulation 2003; 107 (in press): DOI 10.1161/01.CIR.0000044385.60972.AE.

  103. Bengel F, Anton M, Haubner R, et al. In vivo imaging of transgene expression using the herpesviral thymidinekinase reporter gene (HSV1-tk) and radiolabeled FIAU in the rat and pig heart (abstract). Circulation. 2002; 106 (Suppl II):II-331.

    Google Scholar 

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  1. Division of Nuclear Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pa., USA

    Norbert Avril

  2. Nuklearmedizinische Klinik der Technischen Universität München, Klinikum rechts der Isar, Ismaningerstrasse 22, 81675, München, Germany

    Frank M. Bengel

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Avril, N., Bengel, F.M. Defining the success of cardiac gene therapy: how can nuclear imaging contribute?. Eur J Nucl Med Mol Imaging 30, 757–771 (2003). https://doi.org/10.1007/s00259-002-1100-2

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