OSA's Digital Library

Applied Optics

Applied Optics


  • Editor: James C. Wyant
  • Vol. 47, Iss. 31 — Nov. 1, 2008
  • pp: 5944–5952

In vivo fluorescent optical imaging of cytotoxic T lymphocyte migration using IRDye800CW near-infrared dye

Aaron E. Foster, Sunkuk Kwon, Shi Ke, An Lu, Karen Eldin, Eva Sevick-Muraca, and Cliona M. Rooney  »View Author Affiliations

Applied Optics, Vol. 47, Issue 31, pp. 5944-5952 (2008)

View Full Text Article

Enhanced HTML    Acrobat PDF (25714 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



We describe a method to measure in vivo migration of human T cells by using the near-infrared (NIR) dye IRDye800CW. Labeling of Epstein–Barr virus-specific T cells with IRDye800CW did not affect viability, proliferation, or T cell function. Following tail vein injection into mice bearing subcutaneous tumors, the NIR signal could be measured in vivo at the tumor site. Analysis of tumors revealed T cell infiltration and an increased NIR signal, confirming T cell migration. To test specific migration with IRDye800CW, tumors were modified to express CCL5 to measure site-specific migration. The NIR signal was increased at CCL5-secreting tumors compared with control tumors. Together, these data suggest that IRDye800CW may be used to study the trafficking of T cells in a small animal model and may have potential as a short-term reporter molecule for human immunotherapy studies.

© 2008 Optical Society of America

OCIS Codes
(110.3080) Imaging systems : Infrared imaging
(170.0170) Medical optics and biotechnology : Medical optics and biotechnology
(170.1420) Medical optics and biotechnology : Biology
(170.2655) Medical optics and biotechnology : Functional monitoring and imaging

ToC Category:
Medical Optics and Biotechnology

Original Manuscript: June 9, 2008
Revised Manuscript: September 9, 2008
Manuscript Accepted: September 10, 2008
Published: October 31, 2008

Virtual Issues
Vol. 4, Iss. 1 Virtual Journal for Biomedical Optics

Aaron E. Foster, Sunkuk Kwon, Shi Ke, An Lu, Karen Eldin, Eva Sevick-Muraca, and Cliona M. Rooney, "In vivo fluorescent optical imaging of cytotoxic T lymphocyte migration using IRDye800CW near-infrared dye," Appl. Opt. 47, 5944-5952 (2008)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. C. M. Rooney, C. A. Smith, C. Y. Ng, S. Loftin, C. Li, R. A. Krance, M. K. Brenner, and H. E. Heslop, “Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation,” Lancet 345, 9-13 (1995). [CrossRef] [PubMed]
  2. H. E. Heslop, C. Y. Ng, C. Li, C. A. Smith, S. K. Loftin, R. A. Krance, M. K. Brenner, and C. M. Rooney, “Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes,” Nat. Med. 2, 551-555 (1996). [CrossRef] [PubMed]
  3. C. Yee, J. A. Thompson, P. Roche, D. R. Byrd, P. P. Lee, M. Piepkorn, K. Kenyon, M. M. Davis, S. R. Riddell, and P. D. Greenberg, “Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of T cell-mediated vitiligo,” J. Exp. Med. 192, 1637-1644 (2000). [CrossRef] [PubMed]
  4. B. A. Pockaj, R. M. Sherry, J. P. Wei, J. R. Yannelli, C. S. Carter, S. F. Leitman, J. A. Carasquillo, S. M. Steinberg, S. A. Rosenberg, and J. C. Yang, “Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy. Augmentation with cyclophosphamide and correlation with response,” Cancer Res. 73, 1731-1737(1994).
  5. M. S. Mitchell, D. Darrah, D. Yeung, S. Halpern, A. Wallace, J. Voland, V. Jones, and J. Kan-Mitchell, “Phase I trial of adoptive immunotherapy with cytolytic T lymphocytes immunized against a tyrosinase epitope,” J. Clin. Oncol. 20, 1075-1086(2002). [CrossRef] [PubMed]
  6. N. Meidenbauer, J. Marienhagen, M. Laumer, S. Vogl, J. Heymann, R. Andreesen, and A. Mackensen, “Survival and tumor localization of adoptively transferred Melan-A-specific T cells in melanoma patients,” J. Immunol. 170, 2161-2169 (2003). [PubMed]
  7. C. Botti, D. R. Negri, E. Seregni, V. Ramakrishna, F. Arienti, L. Maffioli, C. Lombardo, A. Bogni, C. Pascali, F. Crippa, S. Massaron, F. Remonti, S. Nerini-Molteni, S. Canevari, and E. Bombardieri, “Comparison of three different methods for radiolabelling human activated T lymphocytes,” Eur. J. Nucl. Med. Mol. Imaging 24, 497-504 (1997). [CrossRef]
  8. J. Hardy, M. Edinger, M. H. Bachmann, R. S. Negrin, C. G. Fathman, and C. H. Contag, “Bioluminescence imaging of lymphocyte trafficking in vivo,” Exp. Hematol. 29, 1353-1360 (2001). [CrossRef] [PubMed]
  9. A. Nakajima, C. M. Seroogy, M. R. Sandora, I. H. Tarner, G. L. Costa, C. Taylor-Edwards, M. H. Bachmann, C. H. Contag, and C. G. Fathman, “Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis,” J. Clin. Invest. 107, 1293-1301 (2001). [CrossRef] [PubMed]
  10. G. L. Costa, M. R. Sandora, A. Nakajima, E. V. Nguyen, C. Taylor-Edwards, A. J. Slavin, C. H. Contag, C. G. Fathman, and J. M. Benson, “Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit,” J. Immunol. 167, 2379-2387 (2001). [PubMed]
  11. C. E. Brown, R. P. Vishwanath, B. Aguilar, R. Starr, J. Najbauer, K. S. Aboody, and M. C. Jensen, “Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells,” J. Immunol. 179, 3332-3341 (2007). [PubMed]
  12. J. Vera, B. Savoldo, S. Vigouroux, E. Biagi, M. Pule, C. Rossig, J. Wu, H. E. Heslop, C. M. Rooney, M. K. Brenner, and G. Dotti, “T lymphocytes redirected against the κ light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells,” Blood 108, 3890-3897 (2006). [CrossRef] [PubMed]
  13. B. Ballou, L. A. Ernst, and A. S. Waggoner, “Fluorescence imaging of tumors in vivo,” Curr. Med. Chem. 12, 795-805 (2005). [CrossRef] [PubMed]
  14. A. Moore, J. Grimm, B. Han, and P. Santamaria, “Tracking the recruitment of diabetogenic CD8+ T-cells to the pancreas in real time,” Diabetes 53, 1459-1466 (2004). [CrossRef] [PubMed]
  15. S. A. Anderson, J. Shukaliak-Quandt, E. K. Jordan, A. S. Arbab, R. Martin, H. McFarland, and J. A. Frank, “Magnetic resonance imaging of labeled T-cells in a mouse model of multiple sclerosis,” Ann. Neurol. 55, 654-659 (2004). [CrossRef] [PubMed]
  16. C. Billotey, C. Aspord, O. Beuf, E. Piaggio, F. Gazeau, M. F. Janier, and C. Thivolet, “T-cell homing to the pancreas in autoimmune mouse models of diabetes: in vivo MR imaging,” Radiology (Oak Brook, Ill.) 236, 579-587 (2005). [CrossRef]
  17. G. Koehne, M. Doubrovin, E. Doubrovina, P. Zanzonico, H. F. Gallardo, A. Ivanova, J. Balatoni, J. Teruya-Feldstein, G. Heller, C. May, V. Ponomarev, S. Ruan, R. Finn, R. G. Blasberg, W. Bornmann, I. Riviere, M. Sadelain, R. J. O'Reilly, S. M. Larson, and J. G. Tjuvajev, “Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes,” Nat. Biotechnol. 21, 405-413 (2003). [CrossRef] [PubMed]
  18. M. M. Doubrovin, E. S. Doubrovina, P. Zanzonico, M. Sadelain, S. M. Larson, and R. J. O'Reilly, “In vivo imaging and quantitation of adoptively transferred human antigen-specific T cells transduced to express a human norepinephrine transporter gene,” Cancer Res. 67, 11959-11969 (2007). [CrossRef] [PubMed]
  19. J. V. Frangioni, “In vivo near-infrared fluorescence imaging,” Curr. Opin. Chem. Biol. 7, 626-634 (2003). [CrossRef] [PubMed]
  20. F. K. Swirski, C. R. Berger, J. L. Figueiredo, T. R. Mempel, U. H. von Andrian, M. J. Pittet, and R. Weissleder, “A near-infrared cell tracker reagent for multiscopic in vivo imaging and quantification of leukocyte immune responses,” PLoS ONE 2(10), e1075 (24 October 2007). [CrossRef]
  21. W. Wang, S. Ke, Q. Wu, C. Charnsangavej, M. Gurfinkel, J. G. Gelovani, J. L. Abbruzzese, E. M. Sevick-Muraca, and C. Li, “Near-infrared optical imaging of integrin αvΒ3 in human tumor xenografts,” Mol. Imaging 3, 343-351 (2004). [CrossRef]
  22. J. P. Houston, S. Ke, W. Wang, C. Li, and E. M. Sevick-Muraca, “Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe,” J. Biomed. Opt. 10, 054010 (2005). [CrossRef] [PubMed]
  23. S. Ke, X. Wen, M. Gurfinkel, C. Charnsangavej, S. Wallace, E. M. Sevick-Muraca, and C. Li, “Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts,” Cancer Res. 63, 7870-7875 (2003). [PubMed]
  24. S. Gottschalk, O. L. Edwards, U. Sili, M. H. Huls, T. Goltsova, A. R. Davis, H. E. Heslop, and C. M. Rooney, “Generating CTLs against the subdominant Epstein-Barr virus LMP1 antigen for the adoptive immunotherapy of EBV-associated malignancies,” Blood 101, 1905-1912 (2003). [CrossRef]
  25. S. Kwon, S. Ke, J. P. Houston, W. Wang, Q. Wu, C. Li, and E. M. Sevick-Muraca, “Imaging dose-dependent pharmacokinetics of an RGD-fluorescent dye conjugate targeted to αvΒ3 receptor expressed in Kaposi's sarcoma,” Mol. Imaging 4, 75-87 (2005). [PubMed]
  26. K. E. Adams, S. Ke, S. Kwon, F. Liang, Z. Fan, Y. Lu, K. Hirschi, M. E. Mawad, M. A. Barry, and E. M. Sevick-Muraca, “Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer,” J. Biomed. Opt. 12, 024017 (2007). [CrossRef] [PubMed]
  27. A. M. Leen, U. Sili, B. Savoldo, A. M. Jewell, P. A. Piedra, M. K. Brenner, and C. M. Rooney, “Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications,” Blood 103, 1011-1019 (2003).
  28. C. Hess, T. K. Means, P. Autissier, T. Woodberry, M. Altfeld, M. M. Addo, N. Frahm, C. Brander, B. D. Walker, and A. D. Luster, “IL-8 responsiveness defines a subset of CD8 T cells poised to kill,” Blood 104, 3463-3471 (2004). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

Supplementary Material

» Media 1: AVI (1069 KB)     
» Media 2: AVI (1708 KB)     
» Media 3: AVI (3064 KB)     

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited