Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes.
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.
Koehne
Guenther
G
Allogeneic Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Doubrovin
Mikhail
M
Doubrovina
Ekaterina
E
Zanzonico
Pat
P
Gallardo
Humilidad F
HF
Ivanova
Anna
A
Balatoni
Julius
J
Teruya-Feldstein
Julie
J
Heller
Glenn
G
May
Chad
C
Ponomarev
Vladimir
V
Ruan
Shutian
S
Finn
Ronald
R
Blasberg
Ronald G
RG
Bornmann
William
W
Riviere
Isabelle
I
Sadelain
Michel
M
O'Reilly
Richard J
RJ
Larson
Steven M
SM
Tjuvajev
Juri G Gelovani
JG
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013601:T-Lymphocytes / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000502:physiology; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods; D014161:Transduction, Genetic / Q000379:methods
D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase