Nuclear Medicine and Molecular Imaging

The Korean Society of Nuclear Medicine (대한핵의학회)
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Cardiovascular Molecular Imaging

심장 분자영상

  • Lee, Kyung-Han (Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 이경한 (성균관대학교 의과대학 삼성서울병원 핵의학과)
  • Published : 2009.06.30
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Abstract

Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis, Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field.

Keywords

References

  1. Bengel FM. Noninvasive imaging of cardiac gene expression and its future implications for molecular therapy. Mol Imaging Biol 2005;7:22-9 https://doi.org/10.1007/s11307-005-0923-1
  2. Wu JC, Inubushi M, Sundaresan G, Schelbert HR, Gambhir SS. Optical imaging of cardiac reporter gene expression in living rats. Circulation 2002;105:1631-4 https://doi.org/10.1161/01.CIR.0000014984.95520.AD
  3. Wu JC, Inubushi M, Sundaresan G, Schelbert HR, Gambhir SS. Positron emission tomography imaging of cardiac reporter gene expression in living rats. Circulation 2002;106:180-3 https://doi.org/10.1161/01.CIR.0000023620.59633.53
  4. Lee KH, Kim HK, Paik JY, Matsui T, Choe YS, Choi Y, et al. Accuracy of myocardial sodium/iodide symporter gene expression imaging with radioiodide: evaluation with a dual-gene adenovirus vector. J Nucl Med 2005;46:652-7
  5. Lee KH, Bae JS, Lee SC, Paik JY, Matsui T, Jung KH, et al. Evidence that myocardial Na/I symporter gene imaging does not perturb cardiac function. J Nucl Med 2006;47:1851-7
  6. Wu JC, Chen IY, Wang Y, Tseng JR, Chhabra A, Salek M, et al. Molecular imaging of the kinetics of vascular endothelial growth factor gene expression in ischemic myocardium. Circulation 2004;110:685-91 https://doi.org/10.1161/01.CIR.0000138153.02213.22
  7. Sheikh AY, Wu JC. Molecular imaging of cardiac stem cell transplantation. Curr Cardiol Rep 2006;8:147-54 https://doi.org/10.1007/s11886-006-0026-x
  8. Hung TC, Suzuki K, Urashima T. Multimodality evaluation of the viability of stem cells delivered into different zones of myocardial infarction. Circ Cardiovasc Imaging 2008;1:6-13 https://doi.org/10.1161/CIRCIMAGING.108.767343
  9. 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 https://doi.org/10.1161/01.CIR.0000163546.27639.AA
  10. Aicher A, Brenner W, Zuhayra M, Baadorff 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 https://doi.org/10.1161/01.CIR.0000062649.63838.C9
  11. Kraitchman DL, Heldman AW, Atalar E, Amado LC, Martin BJ, Pittenger MF, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003;107:2290-3 https://doi.org/10.1161/01.CIR.0000070931.62772.4E
  12. 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 https://doi.org/10.1161/01.CIR.0000091252.20010.6E
  13. 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 https://doi.org/10.1161/CIRCULATIONAHA.105.588954
  14. Gyongyosi M, Blanco J, Marian T, et al. Serial non-invasive in vivo PET tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circ Cardiovasc Imaging 2008;1:94-103 https://doi.org/10.1161/CIRCIMAGING.108.797449
  15. Gyongyosi M, Blanco J, Marian T, et al. Serial non-invasive in vivo PET tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circ Cardiovasc Imaging 2008;1:94-103 https://doi.org/10.1161/CIRCIMAGING.108.797449
  16. Wu JC, Spin JM, Cao F, Lin S, Xie X, Gheysens O, et al. Transcriptional profiling of reporter genes used for molecular imaging of embryonic stem cell transplantation. Physiol Genomics 2006;25:29-38 https://doi.org/10.1152/physiolgenomics.00254.2005
  17. Terrovitis J, Kwok KF, Lautarnaki 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 https://doi.org/10.1016/j.jacc.2008.06.051
  18. Jung KH, Paik JY, Koh BH, Lee KH. MAP kinase signaling enhances sodium iodide symporter function and efficacy of radioiodide therapy in non-thyroidal cancer cells. J Nucl Med 2008;49:1966-72 https://doi.org/10.2967/jnumed.108.055764
  19. Jung KH, Paik JY, Lee YL, Lee YJ, Lee JT, Lee KH. Trypsinization severely perturbs radioiodide transport via membrane Nail symporter proteolysis; implications for reporter gene imaging. Nucl Med Biol 2009 (in press)
  20. Choe YS, Lee KH. Targeted in vivo imaging of angiogenesis: present status and perspectives. Curr Pharm Des 2007;13:17-31 https://doi.org/10.2174/138161207779313812
  21. Lu E, Wagner WR, Schellenberger U, Abraham JA, Klibanov AL, Woulfe SR, et al. Targeted in vivo labeling of receptors for vascular endothelial growth factor: approach to identification of ischemic tissue. Circulation 2003;108:97-103 https://doi.org/10.1161/01.CIR.0000079100.38176.83
  22. Rodriguez-Porcel M, Cai W, Gheysens O, Willmann JK, Chen K, Wang H, et al. Imaging of VEGF receptor in a rat myocardial infarction model using PET. J Nucl Med 2008;49:667-73 https://doi.org/10.2967/jnumed.107.040576
  23. Haubner R, Wester H, Reuning U, Senekowitsch-Schmidtke R, Diefenbach B, Kessler H, et al. Radiolabeled ${\alpha}v{\beta}{\beta}$ integrin antagonists: A new class of tracers for tumor targeting. J Nucl Med 1999;40:1061-71
  24. Haubner R, Wester H, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman SL, et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med 2001;42:326-36
  25. Haubner R, Wester H, Weber W, Mang C, Ziegler SI, Goodman SL, et al. Noninvasive imaging of av${\alpha}v{\beta}{\beta}$ integrin expression using $^{18}$F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res 2001;61:1781-5
  26. Jung KH, Lee KH, Paik JY, Ko BH, Bae JS, Lee BC, et al. Favorable biokinetic and tumor-targeting properties of $^{99m}$Tc-labeled glucosamino RGD and effect of Paclitaxel therapy. J Nucl Med 2006;47:2000-7
  27. Lee KH, Jung KH, Song SH, Kim DH, Lee BC, Sung HJ, et al. Radiolabeled RGD uptake and alphav integrin expression is enhanced in ischemic murine hindlimbs. J Nucl Med 2005;46:472-8
  28. Higuchi T, Bengel FM, Seidl S, Watzlowik P, Kessler H, Hegenloh R, et al. Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography. Cardiovasc Res 2008;78:395-403 https://doi.org/10.1093/cvr/cvn033
  29. Meoli DF, Sadeghi MM, Krassilnikova S, Bourke BN, Giordano FJ, Dione DP, et al. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. J Clin Invest 2004;113:1684-91 https://doi.org/10.1172/JCI20352
  30. Kalinowski L, Dobrucki LW, Meoli DF, Dione DP, Sadeghi MM, Madri JA, et al. Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction. J Appl Physiol 2008;104:1504-12 https://doi.org/10.1152/japplphysiol.00861.2007
  31. Sadeghi MM, Krassilnikova S, Zhang J, Gharaei AA, Fassaei HR, Esmailzadeh L, et al. Detection of injury-induced vascular remodeling by targeting activated ${\alpha}v{\beta}{\beta}$ integrin in vivo. Circulation 110:84-90 https://doi.org/10.1161/01.CIR.0000133319.84326.70
  32. Wolters SL, Corsten MF, Reutelingsperger Cp, Narula J, Hofstra L. Cardiovascular molecular imaging of apoptosis. Eur J Nucl Med Mol Imaging 2007;34:S86-98 https://doi.org/10.1007/s00259-007-0443-0
  33. Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev 2002;82:331-71 https://doi.org/10.1152/physrev.00030.2001
  34. Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K, et al. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci USA 1998;95:6349-54 https://doi.org/10.1073/pnas.95.11.6349
  35. Hofstra L, Liem IH, Dumont EA, Boersma HH, van Heerde WL, Doevendans PA, et al. Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet 2000;356:209-12 https://doi.org/10.1016/S0140-6736(00)02482-X
  36. Kietselaer BL, Reutelingsperger CP, Boersma HH, Heidendal GA, Liem IH, Crijns HJ, et al. Noninvasive detection of programmed cell loss with $^{99m}$Tc-labeled annexin A5 in heart failure. J Nucl Med 2007;48:562-7 https://doi.org/10.2967/jnumed.106.039453
  37. Zhao M, Zhu X, Ji S, Zhou J, Ozker KS, Fang W, et al. $^{99m}$Tc-labeled C2A domain of synaptotagmin I as a target-specific molecular probe for noninvasive imaging of acute myocardial infarction. J Nucl Med 2006;47:1367-74
  38. Okada H, Mak TW Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer 2004;4:592-603 https://doi.org/10.1038/nrc1412
  39. Paik JY, Lee KH, Choe YS, Choi Y, Kim BT. Augmented $^{18}$F-FDG uptake in activated monocytes occurs during the priming process and involves tyrosine kinases and protein kinase C. J Nucl Med 2004;45:124-8
  40. Lee SJ, On YK, Lee EJ, Choi JY, Kim BT, Lee KH. Reversal of vascular $^{18}$F-FDG uptake with plasma high-density lipoprotein elevation by atherogenic risk reduction. J Nucl Med 2008;49:1277-82 https://doi.org/10.2967/jnumed.108.052233
  41. Kolodgie FD, Petrov A, Virmani R, Narula Nm Verjan JW, Weber DK, et al. Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque. Circulation 2003;108:3134-9 https://doi.org/10.1161/01.CIR.0000105761.00573.50
  42. Johnson LL, Schofield L, Donahay T, Narula N, Narula J. $^{99m}$Tc-annexin V imaging for in vivo detection of atherosclerotic lesions in porcine coronary arteries. J Nucl Med 2005;46:1186-93
  43. Kietselaer BL, Reutelingsperger Cp, Heidendal GA, Daemen MJ, Mess WH, Hofstra L, et al. Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. N Engl J Med 2004;350:1472-3