Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes Journal Article


Authors: Koehne, G.; Doubrovin, M.; Doubrovina, E.; Zanzonico, P.; Gallardo, H. F.; Ivanova, A.; Balatoni, J.; Teruya-Feldstein, J.; Heller, G.; May, C.; Ponomarev, V.; Ruan, S.; Finn, R.; Blasberg, R. G.; Bornmann, W.; Riviere, I.; Sadelain, M.; O'Reilly, R. J.; Larson, S. M.; Gelovani Tjuvajev, J. G.
Article Title: Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes
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.
Keywords: nonhuman; positron emission tomography; sensitivity and specificity; radiopharmaceuticals; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; allele; animal tissue; cell survival; apoptosis; image analysis; tumor markers, biological; cell line; animal experiment; animal model; tumor xenograft; mice, scid; animalia; transduction, genetic; correlation analysis; antigens; iodine 131; isotope labeling; tissue distribution; iodine radioisotopes; antigen specificity; tomography; tumors; dna viruses; simplexvirus; arabinofuranosyluracil; cell migration; cell movement; cellular distribution; imaging; fialuridine; iodine 124; thymidine kinase; neoplasm transplantation; herpes simplex virus 1; hla antigen; bioaccumulation; epstein barr virus; scintigraphy; tissue; herpesvirus 4, human; cell labeling; tomography, emission-computed; cells; lymphocyte migration; human herpesvirus 4; human herpesvirus 1; humans; priority journal; article
Journal Title: Nature Biotechnology
Volume: 21
Issue: 4
ISSN: 1087-0156
Publisher: Nature Publishing Group  
Date Published: 2003-04-01
Start Page: 405
End Page: 413
Language: English
DOI: 10.1038/nbt805
PUBMED: 12652311
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Chad May
    21 May
  2. Juri Gelovani
    124 Gelovani
  3. William Bornmann
    108 Bornmann
  4. Glenn Heller
    303 Heller
  5. Ronald G Blasberg
    244 Blasberg
  6. Julie T Feldstein
    288 Feldstein
  7. Ronald D Finn
    252 Finn
  8. Guenther Koehne
    175 Koehne
  9. Pat B Zanzonico
    246 Zanzonico
  10. Michel W J Sadelain
    462 Sadelain
  11. Isabelle C Riviere
    168 Riviere
  12. Shutian Ruan
    44 Ruan
  13. Steven M Larson
    779 Larson
  14. Richard O'Reilly
    487 O'Reilly