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

Guenther Koehne, Mikhail Doubrovin, Ekaterina Doubrovina, Pat Zanzonico, Humilidad F. Gallardo, Anna Ivanova, Julius Balatoni, Julie Teruya-Feldstein, Glenn Heller, Chad May, Vladimir Ponomarev, Shutian Ruan, Ronald Finn, Ronald G. Blasberg, William Bornmann, Isabelle Riviere, Michel Sadelain, Richard J. O'Reilly, Steven M. Larson, Juri G. Gelovani Tjuvajev

Research output: Contribution to journalArticlepeer-review

218 Scopus citations

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.

Original languageEnglish
Pages (from-to)405-413
Number of pages9
JournalNature Biotechnology
Volume21
Issue number4
DOIs
StatePublished - 1 Apr 2003
Externally publishedYes

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