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Fluorine-19 Cellular MRI Detection of In Vivo Dendritic Cell Migration and Subsequent Induction of Tumor Antigen-Specific Immunotherapeutic Response |
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| Authors: | Fink Corby Smith Michael Gaudet Jeffrey M Makela Ashley Foster Paula J Dekaban Gregory A |
| Institution: | 1.Molecular Medicine Research Laboratories, Robarts Research Institute and Department of Microbiology and Immunology, University of Western Ontario, 1151 Richmond Street North, London, Ontario, N6A 5B7, Canada ;2.Imaging Research Laboratories, Robarts Research Institute and Department of Medical Biophysics, University of Western Ontario, 1151 Richmond Street North, London, Ontario, N6A 5B7, Canada ; |
| Abstract: | Purpose A major hurdle in the advancement of cell-based cancer immunotherapies is the inability to track in vivo therapeutic cell migration. With respect to dendritic cell (DC)-based cancer immunotherapies, this lack of knowledge represents an even greater hurdle as the quantity of tumor-antigen specific DC reaching a secondary lymphoid organ post injection is predictive of the magnitude of the ensuing tumor-specific immune response. We propose fluorine-19 (F-19) cellular magnetic resonance imaging (MRI) as a suitable and non-invasive imaging modality capable of detecting and quantifying DC migration in vivo and thus, serving as a surrogate marker of DC-based immunotherapeutic effectiveness. ProceduresMurine DC were generated from bone marrow precursors and labeled with a 19F]perfluorocarbon (19F]PFC)-based cell labeling agent. DC were characterized by viability and phenotyping assessments as well as characterized by ability to induce in vivo tumor-specific immune responses following immunization in a B16-F10 mouse model of melanoma. The in vivo migration of 19F]PFC (PFC)-labeled DC was first compared to control unlabeled DC by microscopy and then measured using F-19 cellular MRI. ResultsCulture conditions were optimized such that >?90 % of DC labeled with PFC without affecting viability, phenotype, and function. This optimization permitted consistent detection of PFC-labeled DC migration using F-19 cellular MRI and resulted in the first successful comparison of in vivo migration between PFC-labeled and control unlabeled therapeutic cells of the same origin. PFC-labeled DC are migration-competent in vivo in a B16-F10 tumor-bearing mouse model. ConclusionsWe report a non-invasive and longitudinal imaging modality capable of detecting and quantifying therapeutic cell migration at both 9.4 and 3 Tesla (T) and suitable for therapeutic cell tracking in a tumor-bearing mouse model. F-19 MRI cell tracking is broadly applicable across disease states and is conducive to clinical translation. |
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