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

Nat Biotechnol. 2003 Apr;21(4):405-13. doi: 10.1038/nbt805. Epub 2003 Mar 24.


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-beta-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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Arabinofuranosyluracil / analogs & derivatives*
  • Arabinofuranosyluracil / pharmacokinetics*
  • Biomarkers, Tumor / metabolism
  • Cell Line
  • Cell Movement
  • Cell Survival / physiology
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / metabolism
  • Humans
  • Iodine Radioisotopes / pharmacokinetics*
  • Isotope Labeling / methods
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Radiopharmaceuticals / pharmacokinetics*
  • Sensitivity and Specificity
  • Simplexvirus / enzymology
  • Simplexvirus / genetics
  • T-Lymphocytes / diagnostic imaging*
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / physiology
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Tissue Distribution
  • Tomography, Emission-Computed / methods
  • Transduction, Genetic / methods


  • Biomarkers, Tumor
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Arabinofuranosyluracil
  • fialuridine
  • Thymidine Kinase