Skip to main content
Log in

Cardiac Stem Cell Imaging by SPECT and PET

  • Cardiac Nuclear Imaging (A Cuocolo, Section Editor)
  • Published:
Current Cardiovascular Imaging Reports Aims and scope Submit manuscript

Abstract

After the initial enthusiasm of the preclinical studies of stem cell therapy (SCT) for cardiac diseases a rather rapid translation into clinical trials was accompanied by inconsistent results and at best modest benefit. This has lead to a reverse translation form bedside to bench in order to fully elucidate the fate and mechanism of action of the transplanted cells and find methods to boost their acute engraftment, long term survival and functional effects. Advanced imaging techniques are the only way to achieve this goal in humans. Among them radionuclide imaging is the most mature platform to provide quantitative information on short and long term bio-distribution of the transplanted cells in combination with structural and functional changes of the host organ in clinical practice for the short term future. In this paper we review the contribution of radionuclide imaging in the so far accumulated knowledge regarding SCT for heart diseases, its future potential and challenges.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Chen IY, Wu JC. Cardiovascular molecular imaging: focus on clinical translation. Circulation. 2011;123:425–43.

    PubMed Central  PubMed  Google Scholar 

  2. Finegold JA, Asaria P, Francis DP. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int J Cardiol. 2013;168:934–45.

    PubMed Central  PubMed  Google Scholar 

  3. Li SC, Acevedo J, Wang L, Jiang H, Luo J, Pestell RG, et al. Mechanisms for progenitor cell-mediated repair for ischemic heart injury. Curr Stem Cell Res Ther. 2012;7:2–14.

    PubMed  CAS  Google Scholar 

  4. Segers VF, Lee RT. Stem-cell therapy for cardiac disease. Nature. 2008;451:937–42.

    PubMed  CAS  Google Scholar 

  5. Strauer BE, Steinhoff G. 10 years of intracoronary and intramyocardial bone marrow stem cell therapy of the heart: from the methodological origin to clinical practice. J Am Coll Cardiol. 2011;58:1095–104.

    PubMed  Google Scholar 

  6. Chan AT, Abraham MR. SPECT and PET to optimize cardiac stem cell therapy. J Nucl Cardiol. 2012;19:118–25.

    PubMed  Google Scholar 

  7. Beeres SL, Bengel FM, Bartunek J, Atsma DE, Hill JM, Vanderheyden M, et al. Role of imaging in cardiac stem cell therapy. J Am Coll Cardiol. 2007;49:1137–48.

    PubMed  Google Scholar 

  8. Plewka M, Krzeminska-Pakula M, Lipiec P, Peruga JZ, Jezewski T, Kidawa M, et al. Effect of intracoronary injection of mononuclear bone marrow stem cells on left ventricular function in patients with acute myocardial infarction. Am J Cardiol. 2009;104:1336–42.

    PubMed  Google Scholar 

  9. Meluzin J, Mayer J, Groch L, Janousek S, Hornacek I, Hlinomaz O, et al. Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function. Am Heart J. 2006;152:975 e979-915.

    Google Scholar 

  10. Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol. 2004;94:92–5.

    PubMed  Google Scholar 

  11. Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006;355:1222–32.

    PubMed  CAS  Google Scholar 

  12. Huikuri HV, Kervinen K, Niemela M, Ylitalo K, Saily M, Koistinen P, et al. Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction. Eur Heart J. 2008;29:2723–32.

    PubMed  Google Scholar 

  13. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, et al. Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J. 2006;27:2775–83.

    PubMed  Google Scholar 

  14. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006;355:1210–21.

    PubMed  CAS  Google Scholar 

  15. Cao F, Sun D, Li C, Narsinh K, Zhao L, Li X, et al. Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4 years follow-up. Eur Heart J. 2009;30:1986–94.

    PubMed Central  PubMed  Google Scholar 

  16. Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation. 2008;117:1189–200.

    PubMed  Google Scholar 

  17. Beitnes JO, Hopp E, Lunde K, Solheim S, Arnesen H, Brinchmann JE, et al. Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study. Heart. 2009;95:1983–9.

    PubMed  CAS  Google Scholar 

  18. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355:1199–209.

    PubMed  CAS  Google Scholar 

  19. Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet. 2006;367:113–21.

    PubMed  Google Scholar 

  20. Roncalli J, Mouquet F, Piot C, Trochu JN, Le Corvoisier P, Neuder Y, et al. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial. Eur Heart J. 2011;32:1748–57.

    PubMed Central  PubMed  Google Scholar 

  21. van der Laan A, Hirsch A, Nijveldt R, van der Vleuten PA, van der Giessen WJ, Doevendans PA, et al. Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results. Neth Heart J. 2008;16:436–9.

    PubMed Central  PubMed  Google Scholar 

  22. Tendera M, Wojakowski W, Ruzyllo W, Chojnowska L, Kepka C, Tracz W, et al. Intracoronary infusion of bone marrow-derived selected CD34 + CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. Eur Heart J. 2009;30:1313–21.

    PubMed  Google Scholar 

  23. Traverse JH, Henry TD, Pepine CJ, Willerson JT, Zhao DX, Ellis SG, et al. Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial. JAMA. 2012;308:2380–9.

    PubMed Central  PubMed  CAS  Google Scholar 

  24. Traverse JH, Henry TD, Ellis SG, Pepine CJ, Willerson JT, Zhao DX, et al. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial. JAMA. 2011;306:2110–9.

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Perin EC, Willerson JT, Pepine CJ, Henry TD, Ellis SG, Zhao DX, et al. Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial. JAMA. 2012;307:1717–26.

    PubMed Central  PubMed  CAS  Google Scholar 

  26. Surder D, Manka R, Lo Cicero V, Moccetti T, Rufibach K, Soncin S, et al. Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function. Circulation. 2013;127:1968–79.

    PubMed  Google Scholar 

  27. Kang HJ, Kim MK, Lee HY, Park KW, Lee W, Cho YS, et al. Five-year results of intracoronary infusion of the mobilized peripheral blood stem cells by granulocyte colony-stimulating factor in patients with myocardial infarction. Eur Heart J. 2012;33:3062–9.

    PubMed  Google Scholar 

  28. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004;364:141–8.

    PubMed  Google Scholar 

  29. Meyer GP, Wollert KC, Lotz J, Pirr J, Rager U, Lippolt P, et al. Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial. Eur Heart J. 2009;30:2978–84.

    PubMed  Google Scholar 

  30. Delewi R, Andriessen A, Tijssen JG, Zijlstra F, Piek JJ, Hirsch A. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a meta-analysis of randomised controlled clinical trials. Heart. 2013;99:225–32.

    PubMed  Google Scholar 

  31. Fisher SA, Doree C, Brunskill SJ, Mathur A, Martin-Rendon E. Bone marrow stem cell treatment for ischemic heart disease in patients with no option of revascularization: a systematic review and meta-analysis. PLoS One. 2013;8:e64669.

    PubMed Central  PubMed  CAS  Google Scholar 

  32. Clifford DM, Fisher SA, Brunskill SJ, Doree C, Mathur A, Watt S, et al. Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev. 2012;2, CD006536.

    PubMed  Google Scholar 

  33. Ruggiero A, Thorek DL, Guenoun J, Krestin GP, Bernsen MR. Cell tracking in cardiac repair: what to image and how to image. Eur Radiol. 2012;22:189–204.

    PubMed Central  PubMed  Google Scholar 

  34. Fu Y, Kedziorek D, Kraitchman DL. Recent developments and future challenges on imaging for stem cell research. J Cardiovasc Transl Res. 2010;3:24–9.

    PubMed Central  PubMed  Google Scholar 

  35. Zen K, Okigaki M, Hosokawa Y, Adachi Y, Nozawa Y, Takamiya M, et al. Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response. J Mol Cell Cardiol. 2006;40:799–809.

    PubMed  CAS  Google Scholar 

  36. Kuliszewski MA, Fujii H, Liao C, Smith AH, Xie A, Lindner JR, et al. Molecular imaging of endothelial progenitor cell engraftment using contrast-enhanced ultrasound and targeted microbubbles. Cardiovasc Res. 2009;83:653–62.

    PubMed Central  PubMed  CAS  Google Scholar 

  37. Bara C, Ghodsizad A, Niehaus M, Makoui M, Piechaczek C, Martin U, et al. In vivo echocardiographic imaging of transplanted human adult stem cells in the myocardium labeled with clinically applicable CliniMACS nanoparticles. J Am Soc Echocardiogr. 2006;19:563–8.

    PubMed  Google Scholar 

  38. Mathiasen AB, Kastrup J. Non-invasive in-vivo imaging of stem cells after transplantation in cardiovascular tissue. Theranostics. 2013;3:561–72.

    PubMed Central  PubMed  CAS  Google Scholar 

  39. Fu Y, Azene N, Xu Y, Kraitchman DL. Tracking stem cells for cardiovascular applications in vivo: focus on imaging techniques. Imaging Med. 2011;3:473–86.

    PubMed Central  PubMed  Google Scholar 

  40. Bindslev L, Haack-Sorensen M, Bisgaard K, Kragh L, Mortensen S, Hesse B, et al. Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging: effect on cell proliferation and differentiation. Eur J Nucl Med Mol Imaging. 2006;33:1171–7.

    PubMed  CAS  Google Scholar 

  41. Kircher MF, Gambhir SS, Grimm J. Noninvasive cell-tracking methods. Nat Rev Clin Oncol. 2011;8:677–88.

    PubMed  CAS  Google Scholar 

  42. Gyongyosi M, Blanco J, Marian T, Tron L, Petnehazy O, Petrasi Z, et al. Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circ Cardiovasc Imaging. 2008;1:94–103.

    PubMed Central  PubMed  Google Scholar 

  43. Wu JC, Chen IY, Sundaresan G, Min JJ, De A, Qiao JH, et al. Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography. Circulation. 2003;108:1302–5.

    PubMed  Google Scholar 

  44. Cao F, Lin S, Xie X, Ray P, Patel M, Zhang X, et al. In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation. 2006;113:1005–14.

    PubMed  Google Scholar 

  45. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003;302:415–9.

    PubMed  CAS  Google Scholar 

  46. 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;99:3030–5.

    PubMed Central  PubMed  CAS  Google Scholar 

  47. Wu JC, Tseng JR, Gambhir SS. Molecular imaging of cardiovascular gene products. J Nucl Cardiol. 2004;11:491–505.

    PubMed  Google Scholar 

  48. Bengel FM, Schachinger V, Dimmeler S. Cell-based therapies and imaging in cardiology. Eur J Nucl Med Mol Imaging. 2005;32 Suppl 2:S404–16.

    PubMed  Google Scholar 

  49. Coenegrachts K, De Geeter F, ter Beek L, Walgraeve N, Bipat S, Stoker J, et al. Comparison of MRI (including SS SE-EPI and SPIO-enhanced MRI) and FDG-PET/CT for the detection of colorectal liver metastases. Eur Radiol. 2009;19:370–9.

    PubMed  Google Scholar 

  50. Brenner W, Aicher A, Eckey T, Massoudi S, Zuhayra M, Koehl U, et al. 111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model. J Nucl Med. 2004;45:512–8.

    PubMed  CAS  Google Scholar 

  51. Nowak B, Weber C, Schober A, Zeiffer U, Liehn EA, von Hundelshausen P, et al. Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells. Eur J Nucl Med Mol Imaging. 2007;34:715–21.

    PubMed  CAS  Google Scholar 

  52. Yoon JK, Park BN, Shim WY, Shin JY, Lee G, Ahn YH. In vivo tracking of 111In-labeled bone marrow mesenchymal stem cells in acute brain trauma model. Nucl Med Biol. 2010;37:381–8.

    PubMed  CAS  Google Scholar 

  53. Kollaros N, Theodorakos A, Manginas A, Kitziri E, Katsikis A, Cokkinos D, et al. Bone marrow stem cell adherence into old anterior myocardial infarction: a scintigraphic study using Tl-201 and Tc-99m-HMPAO. Ann Nucl Med. 2012;26:228–33.

    PubMed  Google Scholar 

  54. Aicher A, Brenner W, Zuhayra M, Badorff C, Massoudi S, Assmus B, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation. 2003;107:2134–9.

    PubMed  Google Scholar 

  55. Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation. 2003;108:863–8.

    PubMed  Google Scholar 

  56. Chin BB, Nakamoto Y, Bulte JW, Pittenger MF, Wahl R, Kraitchman DL. 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun. 2003;24:1149–54.

    PubMed  CAS  Google Scholar 

  57. Hou D, Youssef EA, Brinton TJ, Zhang P, Rogers P, Price ET, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation. 2005;112:I150–6.

    PubMed  Google Scholar 

  58. Tran N, Li Y, Maskali F, Antunes L, Maureira P, Laurens MH, et al. Short-term heart retention and distribution of intramyocardial delivered mesenchymal cells within necrotic or intact myocardium. Cell Transplant. 2006;15:351–8.

    PubMed  Google Scholar 

  59. Terrovitis J, Lautamaki R, Bonios M, Fox J, Engles JM, Yu J, et al. Noninvasive quantification and optimization of acute cell retention by in vivo positron emission tomography after intramyocardial cardiac-derived stem cell delivery. J Am Coll Cardiol. 2009;54:1619–26.

    PubMed Central  PubMed  Google Scholar 

  60. Chapon C, Jackson JS, Aboagye EO, Herlihy AH, Jones WA, Bhakoo KK. An in vivo multimodal imaging study using MRI and PET of stem cell transplantation after myocardial infarction in rats. Mol Imaging Biol. 2009;11:31–8.

    PubMed  Google Scholar 

  61. Mitchell AJ, Sabondjian E, Sykes J, Deans L, Zhu W, Lu X, et al. Comparison of initial cell retention and clearance kinetics after subendocardial or subepicardial injections of endothelial progenitor cells in a canine myocardial infarction model. J Nucl Med. 2010;51:413–7.

    PubMed  Google Scholar 

  62. Bonios M, Terrovitis J, Chang CY, Engles JM, Higuchi T, Lautamaki R, et al. Myocardial substrate and route of administration determine acute cardiac retention and lung bio-distribution of cardiosphere-derived cells. J Nucl Cardiol. 2011;18:443–50. Acute cardiac retention and lung bio-distribution vary with the myocardial substrate and injection route.

    PubMed  Google Scholar 

  63. Sabondjian E, Mitchell AJ, Wisenberg G, White J, Blackwood KJ, Sykes J, et al. Hybrid SPECT/cardiac-gated first-pass perfusion CT: locating transplanted cells relative to infarcted myocardial targets. Contrast Media Mol Imaging. 2012;7:76–84.

    PubMed  CAS  Google Scholar 

  64. Gu M, Nguyen PK, Lee AS, Xu D, Hu S, Plews JR, et al. Microfluidic single-cell analysis shows that porcine induced pluripotent stem cell-derived endothelial cells improve myocardial function by paracrine activation. Circ Res. 2012;111:882–93.

    PubMed Central  PubMed  CAS  Google Scholar 

  65. Lang C, Lehner S, Todica A, Boening G, Franz WM, Bartenstein P, et al. Positron emission tomography based in-vivo imaging of early phase stem cell retention after intramyocardial delivery in the mouse model. Eur J Nucl Med Mol Imaging. 2013;40:1730–8.

    PubMed  Google Scholar 

  66. Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B, et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation. 2005;111:2198–202.

    PubMed  Google Scholar 

  67. Blocklet D, Toungouz M, Berkenboom G, Lambermont M, Unger P, Preumont N, et al. Myocardial homing of nonmobilized peripheral-blood CD34+ cells after intracoronary injection. Stem Cells. 2006;24:333–6.

    PubMed  Google Scholar 

  68. Kang WJ, Kang HJ, Kim HS, Chung JK, Lee MC, Lee DS. Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J Nucl Med. 2006;47:1295–301.

    PubMed  Google Scholar 

  69. Goussetis E, Manginas A, Koutelou M, Peristeri I, Theodosaki M, Kollaros N, et al. Intracoronary infusion of CD133+ and CD133-CD34+ selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: cell isolation, adherence to the infarcted area, and body distribution. Stem Cells. 2006;24:2279–83.

    PubMed  CAS  Google Scholar 

  70. Penicka M, Lang O, Widimsky P, Kobylka P, Kozak T, Vanek T, et al. One-day kinetics of myocardial engraftment after intracoronary injection of bone marrow mononuclear cells in patients with acute and chronic myocardial infarction. Heart. 2007;93:837–41.

    PubMed Central  PubMed  CAS  Google Scholar 

  71. Schachinger V, Aicher A, Dobert N, Rover R, Diener J, Fichtlscherer S, et al. Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation. 2008;118:1425–32.

    PubMed  Google Scholar 

  72. Dedobbeleer C, Blocklet D, Toungouz M, Lambermont M, Unger P, Degaute JP, et al. Myocardial homing and coronary endothelial function after autologous blood CD34+ progenitor cells intracoronary injection in the chronic phase of myocardial infarction. J Cardiovasc Pharmacol. 2009;53:480–5.

    PubMed  CAS  Google Scholar 

  73. Quyyumi AA, Waller EK, Murrow J, Esteves F, Galt J, Oshinski J, et al. CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J. 2011;161:98–105. Clear dose-response relationship for intracoronary delivery of stem cells.

    PubMed  Google Scholar 

  74. Musialek P, Tekieli L, Kostkiewicz M, Majka M, Szot W, Walter Z, et al. Randomized transcoronary delivery of CD34(+) cells with perfusion versus stop-flow method in patients with recent myocardial infarction: early cardiac retention of (9)(9)(m)Tc-labeled cells activity. J Nucl Cardiol. 2011;18:104–16.

    PubMed Central  PubMed  Google Scholar 

  75. Erbs S, Linke A, Adams V, Lenk K, Thiele H, Diederich KW, et al. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study. Circ Res. 2005;97:756–62.

    PubMed  CAS  Google Scholar 

  76. Dib N, Michler RE, Pagani FD, Wright S, Kereiakes DJ, Lengerich R, et al. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation. 2005;112:1748–55.

    PubMed  Google Scholar 

  77. Beeres SL, Bax JJ, Dibbets P, Stokkel MP, Zeppenfeld K, Fibbe WE, et al. Effect of intramyocardial injection of autologous bone marrow-derived mononuclear cells on perfusion, function, and viability in patients with drug-refractory chronic ischemia. J Nucl Med. 2006;47:574–80.

    PubMed  Google Scholar 

  78. Beeres SL, Bax JJ, Kaandorp TA, Zeppenfeld K, Lamb HJ, Dibbets-Schneider P, et al. Usefulness of intramyocardial injection of autologous bone marrow-derived mononuclear cells in patients with severe angina pectoris and stress-induced myocardial ischemia. Am J Cardiol. 2006;97:1326–31.

    PubMed  Google Scholar 

  79. Beeres SL, Bax JJ, Dibbets-Schneider P, Stokkel MP, Fibbe WE, van der Wall EE, et al. Sustained effect of autologous bone marrow mononuclear cell injection in patients with refractory angina pectoris and chronic myocardial ischemia: twelve-month follow-up results. Am Heart J. 2006;152:684.e611–6.

    Google Scholar 

  80. Brehm M, Strauer BE. Stem cell therapy in postinfarction chronic coronary heart disease. Nat Clin Pract Cardiovasc Med. 2006;3 Suppl 1:S101–4.

    PubMed  Google Scholar 

  81. van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, et al. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA. 2009;301:1997–2004.

    PubMed  Google Scholar 

  82. Grajek S, Popiel M, Gil L, Breborowicz P, Lesiak M, Czepczynski R, et al. Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: Impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation. Eur Heart J. 2010;31:691–702.

    PubMed  Google Scholar 

  83. Piepoli MF, Vallisa D, Arbasi M, Cavanna L, Cerri L, Mori M, et al. Bone marrow cell transplantation improves cardiac, autonomic, and functional indexes in acute anterior myocardial infarction patients (Cardiac Study). Eur J Heart Fail. 2010;12:172–80.

    PubMed  Google Scholar 

  84. Tuma J, Fernandez-Vina R, Carrasco A, Castillo J, Cruz C, Carrillo A, et al. Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina. J Transl Med. 2011;9:183.

    PubMed Central  PubMed  Google Scholar 

  85. Perin EC, Silva GV, Henry TD, Cabreira-Hansen MG, Moore WH, Coulter SA, et al. A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF). Am Heart J. 2011;161:1078–87.e3.

    PubMed  Google Scholar 

  86. Maki MT, Koskenvuo JW, Ukkonen H, Saraste A, Tuunanen H, Pietila M, et al. Cardiac function, perfusion, metabolism, and innervation following autologous stem cell therapy for acute st-elevation myocardial infarction. A FINCELL-INSIGHT sub-study with PET and MRI. Front Physiol. 2012;3:6.

    PubMed Central  PubMed  Google Scholar 

  87. Moccetti T, Surder D, Klersy C, Vassalli G, Crljenica C, Rossi MG, et al. Sustained improvement in left ventricular function after bone marrow derived cell therapy in patients with acute ST elevation myocardial infarction. A 5-year follow-up from the Stem Cell Transplantation in Ischaemic Myocardium Study. Swiss Med Wkly. 2012;142:w13632.

    PubMed  Google Scholar 

  88. Robey TE, Saiget MK, Reinecke H, Murry CE. Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol. 2008;45:567–81.

    PubMed Central  PubMed  CAS  Google Scholar 

  89. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation. 2006;113:1287–94.

    PubMed  Google Scholar 

  90. Zhang S, Sun A, Xu D, Yao K, Huang Z, Jin H, et al. Impact of timing on efficacy and safetyof intracoronary autologous bone marrow stem cells transplantation in acute myocardial infarction: a pooled subgroup analysis of randomized controlled trials. Clin Cardiol. 2009;32:458–66.

    PubMed  Google Scholar 

  91. Gholamrezanezhad A, Mirpour S, Ardekani JM, Bagheri M, Alimoghadam K, Yarmand S, et al. Cytotoxicity of 111In-oxine on mesenchymal stem cells: a time-dependent adverse effect. Nucl Med Commun. 2009;30:210–6.

    PubMed  CAS  Google Scholar 

  92. Willmann JK, Paulmurugan R, Rodriguez-Porcel M, Stein W, Brinton TJ, Connolly AJ, et al. Imaging gene expression in human mesenchymal stem cells: from small to large animals. Radiology. 2009;252:117–27.

    PubMed Central  PubMed  Google Scholar 

  93. Terrovitis J, Kwok KF, Lautamaki R, Engles JM, Barth AS, Kizana E, et al. Ectopic expression of the sodium-iodide symporter enables imaging of transplanted cardiac stem cells in vivo by single-photon emission computed tomography or positron emission tomography. J Am Coll Cardiol. 2008;52:1652–60.

    PubMed  Google Scholar 

  94. Wang J, Zhang S, Rabinovich B, Bidaut L, Soghomonyan S, Alauddin MM, et al. Human CD34+ cells in experimental myocardial infarction: long-term survival, sustained functional improvement, and mechanism of action. Circ Res. 2010;106:1904–11.

    PubMed Central  PubMed  CAS  Google Scholar 

  95. Liu J, Narsinh KH, Lan F, Wang L, Nguyen PK, Hu S, et al. Early stem cell engraftment predicts late cardiac functional recovery: preclinical insights from molecular imaging. Circ Cardiovasc Imaging. 2012;5:481–90. Early cell signal as assessed by PET -a surrogate marker for acute cell retention- was found to be predictive of later functional improvement.

    PubMed Central  PubMed  Google Scholar 

  96. van der Bogt KE, Sheikh AY, Schrepfer S, Hoyt G, Cao F, Ransohoff KJ, et al. Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation. 2008;118:S121–9.

    PubMed Central  PubMed  Google Scholar 

  97. Perin EC, Tian M, Marini 3rd FC, Silva GV, Zheng Y, Baimbridge F, et al. Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model. PLoS One. 2011;6:e22949.

    PubMed Central  PubMed  CAS  Google Scholar 

  98. Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, et al. Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res. 2013;112:165–73.

    PubMed  CAS  Google Scholar 

  99. Yaghoubi SS, Jensen MC, Satyamurthy N, Budhiraja S, Paik D, Czernin J, et al. Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nat Clin Pract Oncol. 2009;6:53–8.

    PubMed Central  PubMed  CAS  Google Scholar 

  100. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002;106:3009–17.

    PubMed  Google Scholar 

  101. Dobert N, Britten M, Assmus B, Berner U, Menzel C, Lehmann R, et al. Transplantation of progenitor cells after reperfused acute myocardial infarction: evaluation of perfusion and myocardial viability with FDG-PET and thallium SPECT. Eur J Nucl Med Mol Imaging. 2004;31:1146–51.

    PubMed  Google Scholar 

  102. Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002;106:1913–8.

    PubMed  Google Scholar 

  103. Fuchs S, Satler LF, Kornowski R, Okubagzi P, Weisz G, Baffour R, et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol. 2003;41:1721–4.

    PubMed  Google Scholar 

  104. Fuchs S, Kornowski R, Weisz G, Satler LF, Smits PC, Okubagzi P, et al. Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease. Am J Cardiol. 2006;97:823–9.

    PubMed  Google Scholar 

  105. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003;107:2294–302.

    PubMed  Google Scholar 

  106. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Silva GV, et al. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation. 2004;110:II213–8.

    PubMed  Google Scholar 

  107. Herreros J, Prosper F, Perez A, Gavira JJ, Garcia-Velloso MJ, Barba J, et al. Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. Eur Heart J. 2003;24:2012–20.

    PubMed  Google Scholar 

  108. Kang HJ, Kim HS, Zhang SY, Park KW, Cho HJ, Koo BK, et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet. 2004;363:751–6.

    PubMed  CAS  Google Scholar 

  109. Silva GV, Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, et al. Catheter-based transendocardial delivery of autologous bone-marrow-derived mononuclear cells in patients listed for heart transplantation. Tex Heart Inst J. 2004;31:214–9.

    PubMed Central  PubMed  Google Scholar 

  110. Karpov RS, Popov SV, Markov VA, Suslova TE, Ryabov VV, Poponina YS, et al. Autologous mononuclear bone marrow cells during reparative regeneratrion after acute myocardial infarction. Bull Exp Biol Med. 2005;140:640–3.

    PubMed  CAS  Google Scholar 

  111. Strauer BE, Brehm M, Zeus T, Bartsch T, Schannwell C, Antke C, et al. Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. J Am Coll Cardiol. 2005;46:1651–8.

    PubMed  Google Scholar 

  112. Bartunek J, Vanderheyden M, Vandekerckhove B, Mansour S, De Bruyne B, De Bondt P, et al. Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation. 2005;112:I178–83.

    PubMed  Google Scholar 

  113. Katritsis DG, Sotiropoulou PA, Karvouni E, Karabinos I, Korovesis S, Perez SA, et al. Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv. 2005;65:321–9.

    PubMed  Google Scholar 

  114. Wang J, Najjar A, Zhang S, Rabinovich B, Willerson JT, Gelovani JG, et al. Molecular imaging of mesenchymal stem cell: mechanistic insight into cardiac repair after experimental myocardial infarction. Circ Cardiovasc Imaging. 2012;5:94–101. Evaluation of stem cell differentiation as a mechanism for the beneficial effects of SCT using novel imaging probe.

    PubMed Central  PubMed  Google Scholar 

  115. Johnson LL, Schofield L, Donahay T, Bouchard M, Poppas A, Haubner R. Radiolabeled arginine-glycine-aspartic acid peptides to image angiogenesis in swine model of hibernating myocardium. JACC Cardiovasc Imaging. 2008;1:500–10.

    PubMed Central  PubMed  Google Scholar 

  116. Doyle B, Kemp BJ, Chareonthaitawee P, Reed C, Schmeckpeper J, Sorajja P, et al. Dynamic tracking during intracoronary injection of 18F-FDG-labeled progenitor cell therapy for acute myocardial infarction. J Nucl Med. 2007;48:1708–14.

    PubMed  Google Scholar 

  117. Gerber TC, Gibbons RJ. Weighing the risks and benefits of cardiac imaging with ionizing radiation. JACC Cardiovasc Imaging. 2010;3:528–35.

    PubMed  Google Scholar 

  118. Wang F, Dennis JE, Awadallah A, Solchaga LA, Molter J, Kuang Y, et al. Transcriptional profiling of human mesenchymal stem cells transduced with reporter genes for imaging. Physiol Genomics. 2009;37:23–34.

    PubMed Central  PubMed  Google Scholar 

  119. Thyagarajan B, Liu Y, Shin S, Lakshmipathy U, Scheyhing K, Xue H, et al. Creation of engineered human embryonic stem cell lines using phiC31 integrase. Stem Cells. 2008;26:119–26.

    PubMed  CAS  Google Scholar 

  120. Wang Y, Zhang WY, Hu S, Lan F, Lee AS, Huber B, et al. Genome editing of human embryonic stem cells and induced pluripotent stem cells with zinc finger nucleases for cellular imaging. Circ Res. 2012;111:1494–503.

    PubMed Central  PubMed  CAS  Google Scholar 

  121. Lan F, Liu J, Narsinh KH, Hu S, Han L, Lee AS, et al. Safe genetic modification of cardiac stem cells using a site-specific integration technique. Circulation. 2012;126:S20–8.

    PubMed Central  PubMed  CAS  Google Scholar 

  122. Karow M, Chavez CL, Farruggio AP, Geisinger JM, Keravala A, Jung WE, et al. Site-specific recombinase strategy to create induced pluripotent stem cells efficiently with plasmid DNA. Stem Cells. 2011;29:1696–704.

    PubMed Central  PubMed  CAS  Google Scholar 

  123. Huang J, Lee CC, Sutcliffe JL, Cherry SR, Tarantal AF. Radiolabeling rhesus monkey CD34+ hematopoietic and mesenchymal stem cells with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for microPET imaging. Mol Imaging. 2008;7:1–11.

    PubMed  CAS  Google Scholar 

  124. Templin C, Zweigerdt R, Schwanke K, Olmer R, Ghadri JR, Emmert MY, et al. Transplantation and tracking of human-induced pluripotent stem cells in a pig model of myocardial infarction: assessment of cell survival, engraftment, and distribution by hybrid single photon emission computed tomography/computed tomography of sodium iodide symporter transgene expression. Circulation. 2012;126:430–9. First report demonstrating feasibility of repeated long-term in vivo imaging of viability and tissue distribution and also vascular differentiation and long-term engraftment of hiPSCs in a large-animal model of myocardial infarction.

    PubMed  CAS  Google Scholar 

  125. Fiechter M, Ghadri JR, Sidler M, Martin U, Landmesser U, Kaufmann PA, et al. Cardiac quadruple-fusion imaging: a brief report on a novel integrated multimodality approach for in vivo visualization of transplanted stem cells. Int J Cardiol. 2012;161:62–3.

    PubMed  Google Scholar 

  126. Qiao H, Zhang H, Zheng Y, Ponde DE, Shen D, Gao F, et al. Embryonic stem cell grafting in normal and infarcted myocardium: serial assessment with MR imaging and PET dual detection. Radiology. 2009;250:821–9.

    PubMed Central  PubMed  Google Scholar 

  127. Higuchi T, Anton M, Dumler K, Seidl S, Pelisek J, Saraste A, et al. Combined reporter gene PET and iron oxide MRI for monitoring survival and localization of transplanted cells in the rat heart. J Nucl Med. 2009;50:1088–94.

    PubMed  CAS  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Athanasios Katsikis and Maria Koutelou declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Athanasios Katsikis.

Additional information

This article is part of the Topical Collection on Cardiac Nuclear Imaging

Rights and permissions

Reprints and permissions

About this article

Cite this article

Katsikis, A., Koutelou, M. Cardiac Stem Cell Imaging by SPECT and PET. Curr Cardiovasc Imaging Rep 7, 9265 (2014). https://doi.org/10.1007/s12410-014-9265-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s12410-014-9265-1

Keywords

Navigation