Quantitative imaging of the T cell antitumor response by positron-emission tomography.
We describe a noninvasive, quantitative, and tomographic method to visualize lymphocytes within the whole animal. We used positron-emission tomography (PET) to follow the localization of adoptively transferred immune T lymphocytes. Splenic T cells from animals that had rejected a Moloney murine sarcoma virus/Moloney murine leukemia virus (M-MSV/M-MuLV)-induced tumor were marked with a PET reporter gene, injected into tumor-bearing mice, and imaged in a microPET by using a substrate specific for the reporter. Specific localization of immune T cells to the antigen-positive tumor was detected over time, by sequential imaging of the same animals. Naive T cells did not localize to the tumor site, indicating that preimmunization was required. Autoradiography and immunohistochemistry analysis corroborated the microPET data. The method we have developed can be used to assess the effects of immunomodulatory agents intended to potentiate the immune response to cancer, and can also be useful for the study of other cell-mediated immune responses, including autoimmunity.
Dubey
Purnima
P
Department of Microbiology and Molecular Genetics, Molecular Biology Institute, University of Padua, I-35128 Padua, Italy.
Su
Helen
H
Adonai
Nona
N
Du
Shouying
S
Rosato
Antonio
A
Braun
Jonathan
J
Gambhir
Sanjiv S
SS
Witte
Owen N
ON
D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis; D002465:Cell Movement; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000235:genetics; D008980:Moloney murine sarcoma virus / Q000235:genetics; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology*; D010957:Plasmids / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014055:Tomography, Emission-Computed / Q000379:methods*; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins