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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