Skip to main content

Advertisement

SpringerLink
Log in

In vivo imaging of immune cell trafficking in cancer

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

Abstract

Tumour establishment, progression and regression can be studied in vivo using an array of imaging techniques ranging from MRI to nuclear-based and optical techniques that highlight the intrinsic behaviour of different cell populations in the physiological context. Clinical in vivo imaging techniques and preclinical specific approaches have been used to study, both at the macroscopic and microscopic level, tumour cells, their proliferation, metastasisation, death and interaction with the environment and with the immune system. Fluorescent, radioactive or paramagnetic markers were used in direct protocols to label the specific cell population and reporter genes were used for genetic, indirect labelling protocols to track the fate of a given cell subpopulation in vivo. Different protocols have been proposed to in vivo study the interaction between immune cells and tumours by different imaging techniques (intravital and whole-body imaging). In particular in this review we report several examples dealing with dendritic cells, T lymphocytes and macrophages specifically labelled for different imaging procedures both for the study of their physiological function and in the context of anti-neoplastic immunotherapies in the attempt to exploit imaging-derived information to improve and optimise anti-neoplastic immune-based treatments.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Lewis JS, Achilefu S, Garbow JR, Laforest R, Welch MJ. Small animal imaging. Current technology and perspectives for oncological imaging. Eur J Cancer 2002;38(16):2173–88.

    Article  PubMed  Google Scholar 

  2. Dunn KW, Sutton TA. Functional studies in living animals using multiphoton microscopy. ILAR J 2008;49(1):66–77.

    PubMed  CAS  Google Scholar 

  3. Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS. Molecular imaging in drug development. Nat Rev Drug Discov 2008;7(7):591–607.

    Article  PubMed  CAS  Google Scholar 

  4. Ottobrini L, Ciana P, Biserni A, Lucignani G, Maggi A. Molecular imaging: a new way to study molecular processes in vivo. Mol Cell Endocrinol 2006;246(1–2):69–75.

    Article  PubMed  CAS  Google Scholar 

  5. Lucignani G, Ottobrini L, Martelli C, Rescigno M, Clerici M. Molecular imaging of cell-mediated cancer immunotherapy. Trends Biotechnol 2006;24(9):410–8.

    Article  PubMed  CAS  Google Scholar 

  6. Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 2004;17(7):484–99.

    Article  PubMed  CAS  Google Scholar 

  7. Sandhu A, Handa H, Abe M. Synthesis and applications of magnetic nanoparticles for biorecognition and point of care medical diagnostics. Nanotechnology 2010;21:442001–23.

    Article  PubMed  CAS  Google Scholar 

  8. Bae KH, Lee K, Kim C, Park TG. Surface functionalized hollow manganese oxide nanoparticles for cancer targeted siRNA delivery and magnetic resonance imaging. Biomaterials 2011;32:176–84.

    Article  PubMed  CAS  Google Scholar 

  9. Wolf M, Hull WE, Mier W, Heiland S, Bauder-Wüst U, Kinscherf R, et al. Polyamine-substituted gadolinium chelates: a new class of intracellular contrast agents for magnetic resonance imaging of tumors. J Med Chem 2007;50(1):139–48.

    Article  PubMed  CAS  Google Scholar 

  10. Modo M, Cash D, Mellodew K, Williams SC, Fraser SE, Meade TJ, et al. Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage 2002;17(2):803–11.

    Article  PubMed  Google Scholar 

  11. Modo M, Mellodew K, Cash D, Fraser SE, Meade TJ, Price J, et al. Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study. Neuroimage 2004;21(1):311–7.

    Article  PubMed  Google Scholar 

  12. Shapiro EM, Koretsky AP. Convertible manganese contrast agents for molecular and cellular MRI. Magn Reson Med 2008;60(2):265–9.

    Article  PubMed  Google Scholar 

  13. Arbab AS, Yocum GT, Kalish H, Jordan EK, Anderson SA, Khakoo AY, et al. Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood 2004;104(4):1217–23.

    Article  PubMed  CAS  Google Scholar 

  14. Ottobrini L, Lucignani G, Clerici M, Rescigno M. Assessing cell trafficking by noninvasive imaging techniques: applications in experimental tumor immunology. Q J Nucl Med Mol Imaging 2005;49(4):361–6.

    PubMed  CAS  Google Scholar 

  15. Hoshino A, Fujioka NMK, Suzuki K, Yasuhara M, Yamamoto K. Use of fluorescent quantum dot bioconjugates for cellular imaging of immune cells, cell organelle labeling, and nanomedicine: surface modification regulates biological function, including cytotoxicity. J Artif Organs 2007;10(3):149–57.

    Article  PubMed  CAS  Google Scholar 

  16. Chan WC, Maxwell DJ, Gao X, Bailey RE, Han M, Nie S. Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opin Biotech 2002;13(1):40–6.

    Article  PubMed  CAS  Google Scholar 

  17. Bruchez M Jr, Moronne M, Gin P, Weiss S, Alivisatos AP. Semiconductor nanocrystals as fluorescent biological labels. Science 1998;281(5385):2013–6.

    Article  PubMed  CAS  Google Scholar 

  18. Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small 2008;4(1):26–49.

    Article  PubMed  CAS  Google Scholar 

  19. Shiohara A, Hoshino A, Hanaki K, Suzuki K, Yamamoto K. On the cyto-toxicity caused by quantum dots. Microbiol Immunol 2004;48(9):669–751.

    PubMed  CAS  Google Scholar 

  20. Terasaki M. Fluorescent labeling of endoplasmic reticulum. Methods Cell Biol 1989;29:125–35.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. Ulker O, Genç S, Ateş H, Durak H, Atabey N. 99mTc-HMPAO labelling inhibits cell motility and cell proliferation and induces apoptosis of NC–NC cells. Mutat Res 2007;631(2):69–76.

    PubMed  Google Scholar 

  23. Block SS. Fungitoxicity of the 8-quinolinols. J Agric Food Chem 1955;3(3):229–34.

    Article  CAS  Google Scholar 

  24. Klerk CPW, Overmeer RM, Niers TMH, Versteeg HH, Richel DJ, Buckle T, et al. Validity of bioluminescence measurements for noninvasive in vivo imaging of tumor load in small animals. Biotechniques 2007;43(1 Suppl):7–13, 30.

    Article  PubMed  Google Scholar 

  25. König K. Multiphoton microscopy in life sciences. J Microsc 2000;200(Pt 2):83–104.

    Article  PubMed  Google Scholar 

  26. Pham W, Kobukai S, Hotta C, Gore JC. Dendritic cells; therapy and imaging. Expert Opin Biol Ther 2009;9(5):539–64.

    Article  PubMed  CAS  Google Scholar 

  27. Gilad AA, Ziv K, McMahon MT, van Zijl PCM, Neeman M, Bulte JWM. MRI reporter genes. J Nucl Med 2008;49(12):1905–8.

    Article  PubMed  CAS  Google Scholar 

  28. Bouard D, Alazard-Dany D, Cosset FL. Viral vectors: from virology to transgene expression. Br J Pharmacol 2009;157(2):153–65.

    Article  PubMed  CAS  Google Scholar 

  29. Brutkiewicz S, Mendonca M, Stantz K, Comerford K, Bigsby R, Hutchins G, et al. The expression level of luciferase within tumour cells can alter tumour growth upon in vivo bioluminescence imaging. Luminescence 2007;22(3):221–8.

    Article  PubMed  CAS  Google Scholar 

  30. Sakurai H, Kawabata K, Sakurai F, Nakagawa S, Mizuguchi H. Innate immune response induced by gene delivery vectors. Int J Pharm 2008;354(1–2):9–15.

    Article  PubMed  CAS  Google Scholar 

  31. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med 1996;125:605–13.

    PubMed  CAS  Google Scholar 

  32. Lucignani G. Imaging biomarkers: from research to patient care—a shift in view. Eur J Nucl Med Mol Imaging 2007;34:1693–7.

    Article  PubMed  Google Scholar 

  33. Neves AA, Brindle KM. Assessing responses to cancer therapy using molecular imaging. Biochim Biophys Acta 2006;1766:242–61.

    PubMed  CAS  Google Scholar 

  34. Lanzavecchia A, Sallusto F. Regulation of T cell immunity by dendritic cells. Cell 2001;106(3):263–6.

    Article  PubMed  CAS  Google Scholar 

  35. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392(6673):245–52.

    Article  PubMed  CAS  Google Scholar 

  36. O’Neill DW, Bhardwaj N. Exploiting dendritic cells for active immunotherapy of cancer and chronic infections. Mol Biotechnol 2007;36:131–41.

    Article  PubMed  CAS  Google Scholar 

  37. Gilboa E. DC-based cancer vaccines. J Clin Invest 2007;117(5):1195–203.

    Article  PubMed  CAS  Google Scholar 

  38. Mellman I, Steinman RM. Dendritic cells: specialized and regulated antigen processing machines. Cell 2001;106(3):255–8.

    Article  PubMed  CAS  Google Scholar 

  39. Seliger B. Molecular mechanisms of MHC class I abnormalities and APM components in human tumors. Cancer Immunol Immunother 2008;57:1719–26.

    Article  PubMed  CAS  Google Scholar 

  40. de Vries IJ, Lesterhuis WJ, Barentsz JO, Verdijk P, van Krieken JH, Boerman OC, et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 2005;23(11):1407–13.

    Article  PubMed  CAS  Google Scholar 

  41. Geiger JD, Hutchinson RJ, Hohenkirk LF, McKenna EA, Yanik GA, Levine JE, et al. Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res 2001;61(23):8513–9.

    PubMed  CAS  Google Scholar 

  42. Yamanaka R. Dendritic-cell- and peptide-based vaccination strategies for glioma. Neurosurg Rev 2009;32(3):265–73.

    Article  PubMed  Google Scholar 

  43. Rescigno M, Winzler C, Delia D, Mutini C, Lutz MB, Ricciardi-Castagnoli P. Dendritic cell maturation is required for initiation of the immune response. J Leukoc Biol 1997;61(4):415–21.

    PubMed  CAS  Google Scholar 

  44. Bousso P. T-cell activation by fendritic cells in the lymph node: lessons from the movies. Nat Rev Immunol 2008;8(9):675–84.

    Article  PubMed  CAS  Google Scholar 

  45. Stoll S, Delon J, Brotz TM, Germain RN. Dynamic imaging of T cell-dendritic cell interactions in lymph nodes. Science 2002;296(5574):1873–6.

    Article  PubMed  Google Scholar 

  46. Hugues S, Fetler L, Bonifaz L, Helft J, Amblard F, Amigorena S. Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity. Nat Immunol 2004;5(12):1235–42.

    Article  PubMed  CAS  Google Scholar 

  47. Kupiec-Weglinski JW, Austyn JM, Morris PJ. Migration pattern of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues. J Exp Med 1988;167(2):632–45.

    Article  PubMed  CAS  Google Scholar 

  48. Suda T, Callahan RJ, Wilkenson RA, van Rooijen N, Schneeberger EE. Interferon-γ reduces Ia+dendritic cell traffic to the lung. J Leukoc Biol 1996;60(4):519–27.

    PubMed  CAS  Google Scholar 

  49. Prince HM, Wall DM, Ritchie D, Honemann D, Harrrison S, Quach H, et al. In vivo tracking of dendritic cells in patients with multiple myeloma. J Immunother 2008;31(2):166–79.

    Article  PubMed  Google Scholar 

  50. Ruiz A, Nomdedeu M, Ortega M, Lejeune M, Setoain J, Climent N, et al. Assessment of migration of HIV-1-loaded dendritic cells labeled with 111In-oxine used as a therapeutic vaccine in HIV-1-infected patients. Immunotherapy 2009;1(3):347–54.

    Article  PubMed  CAS  Google Scholar 

  51. Blocklet D, Toungouz M, Kiss R, Lambermont M, Velu T, Duriau D, et al. 111In-oxine and 99mTc-HMPAO labelling of antigen-loaded dendritic cells: in vivo imaging and influence on motility and actin content. Eur J Nucl Med Mol Imaging 2003;30(3):440–7.

    Article  PubMed  CAS  Google Scholar 

  52. Verdijk P, Aarntzen EH, Lesterhuis WJ, Boullart AC, Kok E, van Rossum MM, et al. Limited amounts of dendritic cells migrate into the T-cell area of lymph nodes but have high immune activating potential in melanoma patients. Clin Cancer Res 2009;15(7):2531–40.

    Article  PubMed  CAS  Google Scholar 

  53. Olasz EB, Lang L, Seidel J, Green MJ, Eckelman WC, Katz SI. Fluorine-18 labeled mouse bone marrow-derived dendritic cells can be detected in vivo by high resolution projection imaging. J Immunol Methods 2002;260(1–2):137–48.

    Article  PubMed  CAS  Google Scholar 

  54. Thakur ML, Lavender JP, Arnot RN, Silvester DJ, Segal AW. Indium-111-labeled autologous leukocytes in man. J Nucl Med 1977;18:1014–21.

    PubMed  CAS  Google Scholar 

  55. Helfer BM, Balducci A, Nelson AD, Janjic JM, Gil RR, Kalinski P, et al. Functional assessment of human dendritic cells labeled for in vivo (19)F magnetic resonance imaging cell tracking. Cytotherapy 2010;12(2):238–50.

    Article  PubMed  CAS  Google Scholar 

  56. Ahrens ET, Flores R, Xu H, Morel PA. In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol 2005;23(8):983–7.

    Article  PubMed  CAS  Google Scholar 

  57. Krafft MP. Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research. Adv Drug Deliv Rev 2001;47(2–3):209–28.

    Article  PubMed  CAS  Google Scholar 

  58. Castro O, Nesbitt AE, Lyles D. Effect of a perfluorocarbon emulsion (Fluosol-DA) on reticuloendothelial system clearance function. Am J Hematol 1984;16:15–21.

    Article  PubMed  CAS  Google Scholar 

  59. Swirski FK, Berger CR, Figueiredo JL, Mempel TR, von Andrian UH, Pittet MJ, et al. A near-infrared cell tracker reagent for multiscopic in vivo imaging and quantification of leukocyte immune responses. PLoS One 2007;2(10):e1075.

    Article  PubMed  CAS  Google Scholar 

  60. Noh YW, Lim YT, Chung BH. Noninvasive imaging of dendritic cell migration into lymph nodes using near-infrared fluorescent semiconductor nanocrystals. FASEB J 2008;22(11):3908–18.

    Article  PubMed  CAS  Google Scholar 

  61. Schimmelpfennig CH, Schulz S, Arber C, Baker J, Tarner I, McBride J, et al. Ex vivo expanded dendritic cells home to T-cell zones of lymphoid organs and survive in vivo after allogeneic bone marrow transplantation. Am J Pathol 2005;167(5):1321–31.

    Article  PubMed  CAS  Google Scholar 

  62. Ridolfi R, Riccobon A, Galassi R, Giorgetti G, Petrini M, Fiamminghi L, et al. Evaluation of in vivo labelled dendritic cell migration in cancer patients. J Transl Med 2004;2(1):27–37.

    Article  PubMed  CAS  Google Scholar 

  63. Quillien V, Moisan A, Carsin A, Lesimple T, Lefeuvre C, Adamski H, et al. Biodistribution of radiolabelled human dendritic cells injected by various routes. Eur J Nucl Med Mol Imaging 2005;32(7):731–41.

    Article  PubMed  CAS  Google Scholar 

  64. Baumjohann D, Hess A, Budinsky L, Brune K, Schuler G, Lutz MB. In vivo magnetic resonance imaging of dendritic cell migration into the draining lymph nodes of mice. Eur J Immunol 2006;36(9):2544–55.

    Article  PubMed  CAS  Google Scholar 

  65. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420(6917):860–7.

    Article  PubMed  CAS  Google Scholar 

  66. Allavena P, Sica A, Garlanda C, Mantovani A. The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev 2008;222:155–61.

    Article  PubMed  CAS  Google Scholar 

  67. Bunt SK, Yang L, Sinha P, Clements VK, Leips J, Ostrand-Rosenberg S. Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 2007;67(20):10019–26.

    Article  PubMed  CAS  Google Scholar 

  68. Sunderkötter C, Goebeler M, Schulze-Osthoff K, Bhardwaj R, Sorg C. Macrophage-derived angiogenesis factors. Pharmacol Ther 1991;51(2):195–216.

    Article  PubMed  Google Scholar 

  69. Lesimple T, Moisan A, Carsin A, Ollivier I, Mousseau M, Meunier B, et al. Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects. Cancer Immunol Immunother 2003;52(7):438–44.

    Article  PubMed  CAS  Google Scholar 

  70. Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 2001;193(6):727–40.

    Article  PubMed  CAS  Google Scholar 

  71. Wall l, Burke F, Barton C, Smyth J, Balkwill F. IFN-gamma induces apoptosis in ovarian cancer cells in vivo and in vitro. Clin Cancer Res 2003;9(7):2487–96.

    PubMed  CAS  Google Scholar 

  72. Watkins SK, Egilmez NK, Suttles J, Stout RD. IL-12 rapidly alters the functional profile of tumor-associated and tumor-infiltrating macrophages in vitro and in vivo. J Immunol 2007;178(3):1357–62.

    PubMed  CAS  Google Scholar 

  73. Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O’Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 1993;260(5107):547–9.

    Article  PubMed  CAS  Google Scholar 

  74. Clerici M, Clerici E, Shearer GM. The tumor enhancement phenomenon: reinterpretation from a Th1/Th2 perspective. J Natl Cancer Inst 1996;88(7):461–2.

    Article  PubMed  CAS  Google Scholar 

  75. Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, et al. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 2007;67(6):2649–56.

    Article  PubMed  CAS  Google Scholar 

  76. Wyckoff J, Wang W, Lin EJ, Wang Y, Pixley F, Stanley ER. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 2004;64(19):7022–9.

    Article  PubMed  CAS  Google Scholar 

  77. Satoh T, Saika T, Ebara S, Kusaka N, Timme TL, Yang G, et al. Macrophages transduced with an adenoviral vector expressing interleukin 12 suppress tumor growth and metastasis in a preclinical metastatic prostate cancer model. Cancer Res 2003;63(22):7853–60.

    PubMed  CAS  Google Scholar 

  78. 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.

    Article  PubMed  CAS  Google Scholar 

  79. Pittet MJ, Swirski FK, Reynolds F, Josephson L, Weissleder R. Labeling of immune cells for in vivo imaging using magnetofluorescent nanoparticles. Nat Protoc 2006;1(1):73–9.

    Article  PubMed  CAS  Google Scholar 

  80. Leimgruber A, Berger C, Cortez-Retamozo V, Etzrodt M, Newton AP, Waterman P, et al. Behavior of endogenous tumor-associated macrophages assessed in vivo using a functionalized nanoparticle. Neoplasia 2009;11(5):459–68.

    PubMed  CAS  Google Scholar 

  81. Mukherji B, Chakraborty NG, Yamasaki S, Okino T, Yamase H, Sporn JR, et al. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc Natl Acad Sci U S A 1995;92(17):8078–82.

    Article  PubMed  CAS  Google Scholar 

  82. Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998;4(3):328–32.

    Article  PubMed  CAS  Google Scholar 

  83. Lesimple T, Moisan A, Toujas L. Autologous macrophages and anti-tumour cell therapy. Res Immunol 1998;149(7–8):663–71.

    Article  PubMed  CAS  Google Scholar 

  84. Quillien V, Moisan A, Lesimple T, Leberre C, Toujas L. Biodistribution of 111indium-labeled macrophages infused intravenously in patients with renal carcinoma. Cancer Immunol Immunother 2001;50(9):477–82.

    Article  PubMed  CAS  Google Scholar 

  85. Mantovani A, Gavazzi R, Polentarutti N, Spreafico F, Garattini S. Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice. Int J Cancer 1980;25(5):617–20.

    Article  PubMed  CAS  Google Scholar 

  86. Den Otter WF, Dullens FJ. Anti-tumour effects of macrophages injected into animals: a review. In: James K, McBride B, Staurt A, editors. The macrophage and cancer. Edinburgh: Econoprint; 1977. p. 119–141.

  87. Mantovani A. Effects on in vitro tumor growth of murine macrophages isolated from sarcoma lines differing in immunogenicity and metastasizing capacity. Int J Cancer 1978;22(6):741–6.

    Article  PubMed  CAS  Google Scholar 

  88. Kusmartsev S, Gabrilovich DI. Inhibition of myeloid cell differentiation in cancer: the role of reactive oxygen species. J Leukoc Biol 2003;74(2):186–96.

    Article  PubMed  CAS  Google Scholar 

  89. Candido KA, Shimizu K, McLaughlin JC, Kunkel R, Fuller JA, Redman BG, et al. Local administration of dendritic cells inhibits established breast tumor growth: implications for apoptosis-inducing agents. Cancer Res 2001;61(1):228–36.

    PubMed  CAS  Google Scholar 

  90. Durrant LG, Ramage JM. Development of cancer vaccines to activate cytotoxic T lymphocytes. Expert Opin Biol Ther 2005;5(4):555–63.

    Article  PubMed  CAS  Google Scholar 

  91. Rosenberg SA, Dudley ME. Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes. Proc Natl Acad Sci U S A 2004;101 Suppl 2:14639–45.

    Article  PubMed  CAS  Google Scholar 

  92. Piersma SJ, Jordanova ES, van Poelgeest MI, Kwappenberg KM, van der Hulst JM, Drijfhout JW, et al. High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer. Cancer Res 2007;67(1):354–61.

    Article  PubMed  CAS  Google Scholar 

  93. Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, et al. Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 2001;61(13):5132–6.

    PubMed  CAS  Google Scholar 

  94. Talmadge JE, Donkor M, Scholar E. Inflammatory cell infiltration of tumors: Jekyll or Hyde. Cancer Metastasis Rev 2007;26(3–4):373–400.

    Article  PubMed  Google Scholar 

  95. Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber H, et al. Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 2005;201(5):779–91.

    Article  PubMed  CAS  Google Scholar 

  96. Blankenstein T. The role of tumor stroma in the interaction between tumor and immune system. Curr Opin Immunol 2005;17(2):180–6.

    Article  PubMed  CAS  Google Scholar 

  97. Mrass P, Takano H, Ng LG, Daxini S, Lasaro MO, Iparraguirre A, et al. Random migration precedes stable target cell interactions of tumor-infiltrating T cells. J Exp Med 2006;203(12):2749–61.

    Article  PubMed  CAS  Google Scholar 

  98. Boissonnas A, Fetler L, Zeelenberg IS, Hugues S, Amigorena S. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J Exp Med 2007;204(2):345–56.

    Article  PubMed  CAS  Google Scholar 

  99. Cahalan MD, Parker I. Imaging the choreography of lymphocyte trafficking and the immune response. Curr Opin Immunol 2006;18(4):476–82.

    Article  PubMed  CAS  Google Scholar 

  100. Smirnov P, Lavergne E, Gazeau F, Lewin M, Boissonnas A, Doan BT, et al. In vivo cellular imaging of lymphocyte trafficking by MRI: a tumor model approach to cell-based anticancer therapy. Magn Reson Med 2006;56(3):498–508.

    Article  PubMed  CAS  Google Scholar 

  101. Kircher MF, Allport JR, Graves EE, Love V, Josephson L, Lichtman AH, et al. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res 2003;63(20):6838–46.

    PubMed  CAS  Google Scholar 

  102. Lazovic J, Jensen MC, Ferkassian E, Aguilar B, Raubitschek A, Jacobs RE. Imaging immune response in vivo: cytolytic action of genetically altered T cells directed to glioblastoma multiforme. Clin Cancer Res 2008;14(12):3832–9.

    Article  PubMed  CAS  Google Scholar 

  103. Yaghoubi SS, Jensen MC, Satyamurthy N, Budhiraja S, Paik D, Czernin J. Noninvasive detection of therapeutic cytolytic T cells with 18 F-FHBG PET in a patient with glioma. Nat Clin Pract Oncol 2009;6(1):53–8.

    Article  PubMed  CAS  Google Scholar 

  104. Dobrenkov K, Olszewska M, Likar Y, Shenker L, Gunset G, Cai S, et al. Monitoring the efficacy of adoptively transferred prostate cancer-targeted human T lymphocytes with PET and bioluminescence imaging. J Nucl Med 2008;49(7):1162–70.

    Article  PubMed  Google Scholar 

  105. Jansen ED, Pickett PM, Mackanos MA, Virostko J. Effect of optical tissue clearing on spatial resolution and sensitivity of bioluminescence imaging. J Biomed Opt 2006;11(4):041119.

    Article  PubMed  Google Scholar 

  106. Prescher JA, Contag CH. Guided by the light: visualizing biomolecular processes in living animals with bioluminescence. Curr Opin Chem Biol 2010;14:80–9.

    Article  PubMed  CAS  Google Scholar 

  107. Pittet MJ, Grimm J, Berger CR, Tamura T, Wojtkiewicz G, Nahrendorf M, et al. In vivo imaging of T cell delivery to tumors after adoptive transfer therapy. Proc Natl Acad Sci U S A 2007;104(30):12457–61.

    Article  PubMed  CAS  Google Scholar 

  108. Su H, Chang DS, Gambhir SS, Braun J. Monitoring the antitumor response of naive and memory CD8 T cells in RAG1-/- mice by positron-emission tomography. J Immunol 2006;176(7):4459–67.

    PubMed  CAS  Google Scholar 

  109. Gudmundsdottir H, Turka LA. A closer look at homeostatic proliferation of CD4+ T cells: costimulatory requirements and role in memory formation. J Immunol 2001;167(7):3699–707.

    PubMed  CAS  Google Scholar 

  110. Doubrovin MM, Doubrovina ES, Zanzonico P, Sadelain M, Larson SM, O’Reilly R. In vivo imaging and quantitation of adoptively transferred human antigen-specific T cells transduced to express a human norepinephrine transporter gene. Cancer Res 2007;67(24):11959–69.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by the FP6 funded Hi-CAM project (LSHC-CT-2006-037737), PRIN (20082NHWH9) and AIRC (IG2009-9311). The authors are grateful to Ms Catherine Wrenn for her advice and skilful editorial support.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences and Technologies, University of Milan, Milan, Italy

    Luisa Ottobrini, Cristina Martelli, Mario Clerici & Giovanni Lucignani

  2. Centre of Molecular and Cellular Imaging (IMAGO), Milan, Italy

    Luisa Ottobrini, Cristina Martelli, Mario Clerici & Giovanni Lucignani

  3. Department of Clinical Sciences, University of Milan, Milan, Italy

    Daria Lucia Trabattoni

  4. Don C Gnocchi Foundation IRCCS, via Capecelatro 66, 20148, Milan, Italy

    Mario Clerici

  5. Department of Diagnostic Services, Unit of Nuclear Medicine, San Paolo Hospital, Milan, Italy

    Giovanni Lucignani

Authors
  1. Luisa Ottobrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Martelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daria Lucia Trabattoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mario Clerici
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giovanni Lucignani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario Clerici.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ottobrini, L., Martelli, C., Trabattoni, D.L. et al. In vivo imaging of immune cell trafficking in cancer. Eur J Nucl Med Mol Imaging 38, 949–968 (2011). https://doi.org/10.1007/s00259-010-1687-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-010-1687-7

Keywords

Search

Navigation