Advertisement

The Role of Molecular Imaging in Personalized Medicine

  • Michelle Bradbury
Chapter

Abstract

The implementation and integration of systems biology approaches with the emerging nanosciences and microchip technology will profoundly revolutionize molecular imaging and fuel the drive toward a more predictive and individualized health care. In combination with informatics platforms, key gene and protein targets may be identified that will serve as more effective targets for diagnostic and therapeutic interventions. Drug development may additionally be expedited by the judicious selection of more appropriate molecular biomarkers that will serve as objective endpoints of treatment efficacy. Finally, with the more widespread proliferation of high field magnets and advancements in imaging hardware, acquisition methods, and novel, “smart” MR agents, the ability to achieve higher resolution analyses of tumor biology, cell tracking, and gene expression will be more fully realized.

Keywords

Molecular Imaging Gradient Echo Gold Nanoshells Superparamagnetic Iron Oxide Nanoparticles Nanoparticle Probe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Betensky RA, Louis DN, Cairncross JG. Influence of unrecognized molecular heterogeneity on randomized clinical trials. J Clin Oncol. 2002;20:2495–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Hughes T, Branford S. Molecular monitoring of chronic myeloid leukemia. Semin Hematol. 2003;40(2 Suppl 2):62–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, et al. The Connectivity Map: using gene expression signatures to ­connect small molecules, genes, and disease. Science. 2006;313(5795):1929–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Martin M. Molecular biology of breast cancer. Clin Transl Oncol. 2006;8(1):7–14.PubMedCrossRefGoogle Scholar
  5. 5.
    Radich JP, Dai H, Mao M, Oehler V, Schelter J, Druker B, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA. 2006;103(8):2794–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Thrall J. Personalized medicine. Radiology. 2004;231:613–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Kitano H. Systems biology: a brief overview. Science. 2002;295:1662–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Heath JR, Phelps ME, Hood L. NanoSystems biology. Mol Imag Biol. 2003;5(5):312–25.CrossRefGoogle Scholar
  9. 9.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.PubMedCrossRefGoogle Scholar
  10. 10.
    Khalil IG, Hill C. Systems biology for cancer. Curr Opin Oncol. 2005;17(1):44–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Ideker T, Thorsson V, Ranish JA, Christmas R, Buhler J, Eng JK, et al. Integrated genomic and proteomic analyses of a systemically perturbed metabolic network. Science. 2001;292:929–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Lin B, White T, Lu W, Xie T, Utleg AG, Yan X, et al. Evidence for the presence of disease-perturbed networks in prostate cancer cells by genomic and proteomic analyses: a systems approach to disease. Cancer Res. 2005;65(8):3081–91.PubMedGoogle Scholar
  13. 13.
    Hood L, Heath JR, Phelps ME, Lin B. Systems biology and new technologies enable predictive and preventative medicine. Science. 2004;306:640–3.PubMedCrossRefGoogle Scholar
  14. 14.
    Weston AD, Hood L. Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine. J Proteome Res. 2004;3:179–96.PubMedCrossRefGoogle Scholar
  15. 15.
    Hood L, Perlmutter RM. The impact of systems approaches on ­biological problems in drug discovery. Nat Biotechnol. 2004;22(10):1215–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Rudin M, Weissleder R. Molecular imaging in drug discovery and development. Nat Rev Drug Discov. 2003;2:123–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Aebersold R, Anderson L, Caprioli R, Druker B, Hartwell L, Smith R. Perspective: a program to improve protein biomarker discovery for cancer. J Proteome Res. 2005;4(4):1104–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Isaacs JT. The biology of hormone refractory prostate cancer. Why does it develop? Urol Clin North Am. 1999;26:263–73.PubMedCrossRefGoogle Scholar
  19. 19.
    Jain KK. Applications of biochips: from diagnostics to personalized medicine. Curr Opin Drug Discov Devel. 2004;7(3):285–9.PubMedGoogle Scholar
  20. 20.
    Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med. 2003;348:2491–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Li KCP, Pandit SD, Guccione S, Bednarski MD. Molecular imaging applications in nanomedicine. Biomed Microdevices. 2004;6:113–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Sullivan DC, Ferrari M. Nanotechnology and tumor imaging. Mol Imaging. 2004;3(4):364–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Schellenberger EA, Bogdanov A, Hogemann D, Tait J, Weissleder R, Josephson L. Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Mol Imaging. 2002;1(2):102–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Hayflick L. Mortality and immortality at the cellular level. Biochemistry. 1997;62:639–43.Google Scholar
  25. 25.
    Grimm J, Perez JM, Josephson L, Weissleder R. Novel nanosensors for rapid analysis of telomerase activity. Cancer Res. 2004;64:639–43.PubMedCrossRefGoogle Scholar
  26. 26.
    Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;5:161–71.PubMedCrossRefGoogle Scholar
  27. 27.
    Schmieder AH, Winter PM, Caruthers SD, Harris TD, Williams TA, Allen JS, et al. Molecular MR imaging of melanoma angiogenesis with ανβ3-targeted paramagnetic nanoparticles. Magn Reson Med. 2005;53:621–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Winter PM, Lanza GM, Wickline SA. Molecular imaging of angiogenesis in early-stage atherosclerosis with ανβ3-integrin-targeted nanoparticles. Circulation. 2003;108:2270–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KCP. Detection of tumor angiogenesis in vivo by ανβ3-targeted magnetic resonance imaging. Nat Med. 1998;4(5):623–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Anderson SA, Wickline SA, Kotyk JJ. Magnetic resonance contrast enhancement of neovasculature with ανβ3-targeted nanoparticles. Magn Reson Med. 2000;44:433–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Morawski AM, Winter PM, Crowder KC, Caruthers SD, Fuhrhop RW, Scott MJ, et al. Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Reson Med. 2004;51:480–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Smith AM, Dave S, Nie S, True L, Gao X. Multicolor quantum dots for molecular diagnostics of cancer. Expert Rev Mol Diagn. 2006;6(2):231–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Hernandez J, Thompson I. Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker. Cancer. 2004;101(5):894–904.PubMedCrossRefGoogle Scholar
  34. 34.
    Goessl C. Noninvasive molecular detection of cancer- the bench and the bedside. Curr Med Chem. 2003;10(8):691–706.PubMedCrossRefGoogle Scholar
  35. 35.
    Sukhanova A, Devy M, Venteo L, Kaplan H, Artemyev M, Oleinikov V, et al. Biocompatible fluorescent nanocrystals for immunolabeling of membrane proteins and cells. Anal Biochem. 2004;324(1):60–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Sukhanova A, Venteo L, Devy M, Artemyev M, Oleinikov V, Pluot M, et al. Highly stable fluorescent nanocrystals as a novel class of labels for immunohistochemical analysis of paraffin-embedded tissue sections. Lab Invest. 2002;82(9):1259–61.PubMedGoogle Scholar
  37. 37.
    Parak WJ, Boudreau R, LeGros M, Gerion D, Zanchet D, Micheel CM, et al. Cell motility and metastatic potential studies based on quantum dot imaging of phagokinetic tracks. Adv Mater. 2002;14(12):882–5.CrossRefGoogle Scholar
  38. 38.
    Dahan M, Levi S, Luccardini C, Rostaing P, Riveau B, Triller A. Diffusion dynamics of glycine receptors revealed by single quantum dot tracking. Science. 2003;302(5644):442–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Gao X, Yuanyuan C, Levenson RM, Chung LWK, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004;8(22):969–76.CrossRefGoogle Scholar
  40. 40.
    Gao X, Yang L, Petros JA, Marshall FF, Simons JW, Nie S. In vivo molecular and cellular imaging with quantum dots. Curr Opin Biotechnol. 2005;16:63–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Mulder WJM, Koole R, Brandwijk RJ, Storm G, Chin PTK, Strijkers GJ, et al. Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Lett. 2006;6(1):1–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Wu X, Liu H, Liu J, Haley KN, Treadway JA, Larson JP, et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol. 2003;21:41–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Weissleder R, Kelly K, Sun EY, Shtatland T, Josephson L. Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol. 2005;23(11):1418–23.PubMedCrossRefGoogle Scholar
  44. 44.
    Ozkan M. Quantum dots and other nanoparticles: what can they offer to drug discovery? DDT. 2004;9(24):1065–71.PubMedGoogle Scholar
  45. 45.
    Jain KK. The role of nanobiotechnology in drug discovery. DDT. 2005;10(21):1435–42.PubMedGoogle Scholar
  46. 46.
    Fortina P, Kricka LJ, Surrey S, Grodzinski P. Nanobiotechnology: the promise and reality of new approaches to molecular recognition. Trends Biotechnol. 2005;23(4):168–73.PubMedCrossRefGoogle Scholar
  47. 47.
    Hauck TS, Anderson RE, Fischer HC, Newbigging S, Chan W. In vivo quantum dot toxicity assessment. Small. 2010;6:138–44.PubMedCrossRefGoogle Scholar
  48. 48.
    Burns A et al. Fluorescent silica nanoparticles with efficient urinary excretion for nanomedicine. Nano Lett. 2009;9:442–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Burns A, Ow H, Wiesner U. Fluorescent core-shell silica nanoparticles: towards “lab on a particle” architectures for nanobiotechnology. Chem Soc Rev. 2006;35:1028–42.PubMedCrossRefGoogle Scholar
  50. 50.
    Choi J et al. Core-shell silica nanoparticles as fluorescent labels for nanomedicine. J Biomed Opt. 2007;12:064007.PubMedCrossRefGoogle Scholar
  51. 51.
    Kim S, Lim YT, Soltesz EG, DeGrand AM, Lee J, Nakayama A, et al. Near-infrared fluorescent type-II quantum dots for sentinel lymph node mapping. Nat Biotechnol. 2004;22:93–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B, Price RE, et al. Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc Natl Acad Sci USA. 2003;100(23):13549–54.PubMedCrossRefGoogle Scholar
  53. 53.
    Hirsch LR, Jackson JB, Lee A, Halas NJ, West JL. A whole blood immunoassay using gold nanoshells. Anal Chem. 2003;75(10):2377–81.PubMedCrossRefGoogle Scholar
  54. 54.
    Loo C, Lowery A, Halas N, West J, Drezek R. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett. 2005;5(4):709–11.PubMedCrossRefGoogle Scholar
  55. 55.
    Kim J, Park S, Lee JE, Jin SM, Lee JH, Lee IS, et al. Designed fabrication of multifunctional magnetic gold nanoshells and their application to magnetic resonance imaging and photothermal therapy. Angew Chem Int Ed Engl. 2006;45:1–6.CrossRefGoogle Scholar
  56. 56.
    Weissleder R. Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer. 2002;2:11–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 2003;17:545–80.PubMedCrossRefGoogle Scholar
  58. 58.
    Jaffer FA, Weissleder R. Seeing within: molecular imaging of the cardiovascular system. Circ Res. 2004;94:433–45.PubMedCrossRefGoogle Scholar
  59. 59.
    Choudhury RP, Fuster V, Fayad ZA. Molecular, cellular, and functional imaging of atherosclerosis. Nat Rev Drug Discov. 2004;3:913–25.PubMedCrossRefGoogle Scholar
  60. 60.
    Jaffer FA, Weissleder R. Molecular imaging in the clinical arena. JAMA. 2005;293(7):855–62.PubMedCrossRefGoogle Scholar
  61. 61.
    Aboagye EO, Luthra SK, Brady F, Poole K, Anderson H, Jones T, et al. Cancer research UK procedures in manufacture and toxicology of radiotracers intended for pre-phase I positron emission tomography studies in cancer patients. Br J Cancer. 2002;86:1052–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Ichikawa T, Hoegemann D, Saeki Y, Tyminski E, Terada K, Weissleder R, et al. MRI of transgene expression: correlation to therapeutic gene expression. Neoplasia. 2002;4:523–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Kang HW, Josephson L, Petrovsky A, Weissleder R, Bogdanov Jr A. Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconjug Chem. 2002;13:122–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Kircher MF, Allport J, Graves EE, Love V, Josephson L, Lichtman A, et al. In vivo high resolution 3D imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res. 2003;63:6838–46.PubMedGoogle Scholar
  65. 65.
    Kooi ME, Cappendijk VC, Cleutjens KB, Kessels AG, Kitslaar PJ, Borgers M, et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003;107:2453–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Guller U, Nitzsche E, Moch H, Zuber M. Is positron emission tomography an accurate non-invasive alternative to sentinel lymph node biopsy in breast cancer patients? J Natl Cancer Inst. 2003;95:1040–3.PubMedCrossRefGoogle Scholar
  67. 67.
    Mitchell DA, Fecci PE, Sampson JH. Adoptive immunotherapy for malignant gliomas. Cancer J. 2003;9:157–66.PubMedCrossRefGoogle Scholar
  68. 68.
    Kipps TJ. Immune and cell therapy of hematologic malignancies. Int J Hematol. 2002;76:269–73.PubMedCrossRefGoogle Scholar
  69. 69.
    Peaire AE, Takeshima T, Johnston JM, et al. Production of dopaminergic neurons for cell therapy in the treatment of Parkinson’s disease. J Neurosci Methods. 2003;124:61–74.PubMedCrossRefGoogle Scholar
  70. 70.
    Zimmerman WH, Eschenhagen T. Cardiac tissue engineering for replacement therapy. Heart Fail Rev. 2003;8:259–69.CrossRefGoogle Scholar
  71. 71.
    Scharfmann R. Alternative sources of beta cells for cell therapy of diabetes. Eur J Clin Invest. 2003;33:595–600.PubMedCrossRefGoogle Scholar
  72. 72.
    Shaw T, Quan J, Totoritis MC. B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience. Ann Rheum Dis. 2003;62:ii55–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Hanson HL, Donermeyer DL, Ikeda H, et al. Eradication of established tumors by CD8+ T cell adoptive immunotherapy. Immunity. 2002;13:265–76.CrossRefGoogle Scholar
  74. 74.
    Chapman AL, Rickinson AB, Thomas WA, et al. Epstein-Barr virus-specific cytotoxic T lymphocyte responses in the blood and tumor site of Hodgkin’s disease patients: implications for a T cell-based therapy. Cancer Res. 2001;61:6219–26.PubMedGoogle Scholar
  75. 75.
    Yee C, Thompson JA, Byrd D, et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA. 2002;99:16168–73.PubMedCrossRefGoogle Scholar
  76. 76.
    Bulte JWM, Douglas T, Witwer B, et al. Magnetodendrimers allow endosomal magnetic labeling and in vivo cell tracking of stem cells. Nat Biotechnol. 2001;19:1141–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Bulte JWM, Zhang S, van Gelderen P, et al. Neurotransplantation of magnetically-labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci USA. 1999;96:15256–61.PubMedCrossRefGoogle Scholar
  78. 78.
    Hill JM, Dick AJ, Raman VK, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation. 2003;108:1009–14.PubMedCrossRefGoogle Scholar
  79. 79.
    Schellingerhout D, Josephson L. Molecular imaging of cell-based therapies. Neuroimaging Clin N Am. 2004;14:331–42.PubMedCrossRefGoogle Scholar
  80. 80.
    de Vries IJM, Lesterhuis WJ, Barentsz JO, Verdijk P, Han van Krieken J, Boerman OC, et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapies. Nat Biotechnol. 2005;23:1407–13.PubMedCrossRefGoogle Scholar
  81. 81.
    Allport JR, Weissleder R. In vivo imaging of gene and cell therapies. Exp Hematol. 2001;29:1237–46.PubMedCrossRefGoogle Scholar
  82. 82.
    Shah K, Jacobs A, Breakefield XO, et al. Molecular imaging of gene therapy for cancer. Gene Ther. 2004;11:1175–87.PubMedCrossRefGoogle Scholar
  83. 83.
    Ichikawa T, Hogemann D, Saeki Y, et al. MRI of transgene expression: correlation to therapeutic gene expression. Neoplasia. 2002;4(6):523–30.PubMedCrossRefGoogle Scholar
  84. 84.
    Stegman L, Rehemtulla A, Beattie B, et al. Non-invasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy. Proc Natl Acad Sci USA. 1999;96:9821–6.PubMedCrossRefGoogle Scholar
  85. 85.
    Shyu KG, Chang H, Wang BW, et al. Intramuscular vascular endothelial growth factor gene therapy in patients with chronic critical leg ischemia. Am J Med. 2003;114(2):85–92.PubMedCrossRefGoogle Scholar
  86. 86.
    Yu X, Song SK, Chen J, Scott MJ, Fuhrhop RJ, Hall CS, et al. High-resolution MRI characterization of human thrombus using a novel fibrin-targeted nanoparticle contrast agent. Magn Reson Med. 2000;44(6):867–72.PubMedCrossRefGoogle Scholar
  87. 87.
    Flacke S, Fischer S, Scott MJ, Fuhrhop RJ, Allen JS, McLean M, et al. Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaque. Circulation. 2001;104(11):1280–5.PubMedCrossRefGoogle Scholar
  88. 88.
    Johansson LO, Bjornerud A, Ahlstrom HK, Ladd DL, Fuji DK. A targeted contrast agent for magnetic resonance imaging of thrombus: implications of spatial resolution. J Magn Reson Imaging. 2001;13:613–8.CrossRefGoogle Scholar
  89. 89.
    Sirol M, Fuster V, Badimon JJ, Fallon JT, Toussaint JF, Fayad ZA. Chronic thrombus detection with in vivo magnetic resonance imaging and a fibrin-targeted contrast agent. Circulation. 2005;112:1594–600.PubMedCrossRefGoogle Scholar
  90. 90.
    Weinberg R. The Biology of Cancer. New York: Garland Science; 2006.Google Scholar
  91. 91.
    Anderson SA, Glod J, Arbab AS, Noel M, Ashari P, Fine HA, et al. Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model. Blood. 2005;105:420–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of RadiologyMemorial Sloan Kettering Cancer CenterNew YorkUSA

Personalised recommendations