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Abstract

New technologies are needed to characterize the migration, survival, and function of antigen-specific T cells in vivo. Here, we demonstrate that Epstein-Barr virus (EBV)–specific T cells transduced with vectors encoding herpes simplex virus-1 thymidine kinase (HSV-TK) selectively accumulate radiolabeled 2′-fluoro-2′-deoxy-1-β-D-arabinofuranosyl-5-iodouracil (FIAU). After adoptive transfer, HSV-TK+ T cells labeled in vitro or in vivo with [131I]FIAU or [124I]FIAU can be noninvasively tracked in SCID mice bearing human tumor xenografts by serial images obtained by scintigraphy or positron emission tomography (PET), respectively. These T cells selectively accumulate in EBV+ tumors expressing the T cells' restricting HLA allele but not in EBV or HLA-mismatched tumors. The concentrations of transduced T cells detected in tumors and tissues are closely correlated with the concentrations of label retained at each site. Radiolabeled transduced T cells retain their capacity to eliminate targeted tumors selectively. This technique for imaging the migration of ex vivo–transduced antigen-specific T cells in vivo is informative, nontoxic, and potentially applicable to humans.

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Acknowledgements

This work was supported by US National Institutes of Health grants CA59350, P50 CA86438, CA23766, HL53752, CA57599, CA76117, R24 CA83084, Department of Energy grants FG02-02ER63481, FG03-86ER60407, and 95ER62039, a Translational Research Award of the Leukemia and Lymphoma Society, The Aubrey Fund for Pediatric Cancer Research, The Larry H. Smead Fund, and The Vincent Astor Chair Research Fund. We thank Judith Guerrero, Brad Beatty, and Tatiana Beresten for their excellent technical support.

Author information

Author notes

    • Guenther Koehne
    • , Mikhail Doubrovin
    •  & Ekaterina Doubrovina

    These three authors contributed equally to this work.

Affiliations

  1. Allogeneic Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Guenther Koehne
    • , Ekaterina Doubrovina
    •  & Richard J. O'Reilly
  2. Gene Transfer and Somatic Cell Engineering Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Humilidad F. Gallardo
    • , Chad May
    • , Isabelle Riviere
    •  & Michel Sadelain
  3. Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Mikhail Doubrovin
    • , Pat Zanzonico
    • , Vladimir Ponomarev
    • , Ronald G. Blasberg
    • , Steven M. Larson
    •  & Juri G. Gelovani Tjuvajev
  4. Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Mikhail Doubrovin
    • , Anna Ivanova
    • , Vladimir Ponomarev
    • , Ronald G. Blasberg
    •  & Juri G. Gelovani Tjuvajev
  5. Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Guenther Koehne
    • , Ekaterina Doubrovina
    • , Chad May
    • , Isabelle Riviere
    • , Michel Sadelain
    •  & Richard J. O'Reilly
  6. Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Pat Zanzonico
    •  & Shutian Ruan
  7. Radiochemistry Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Julius Balatoni
    •  & Ronald Finn
  8. Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Julie Teruya-Feldstein
  9. Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • Glenn Heller
  10. Preparative Care Resource Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

    • William Bornmann

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The authors declare no competing financial interests.

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Correspondence to Richard J. O'Reilly.

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DOI

https://doi.org/10.1038/nbt805

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