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.
Procedures
Murine 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.
Results
Culture 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.
Conclusions
We 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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Acknowledgments
We thank Dr. Amanda Hamilton and Dr. Kristin Chadwick for technical expertise and Dr. Thomas Craig Meagher for assistance with manuscript reviewing.
Funding
This research was supported by a grant from the Ontario Institute for Cancer Research.
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Fink, C., Smith, M., Gaudet, J.M. et al. Fluorine-19 Cellular MRI Detection of In Vivo Dendritic Cell Migration and Subsequent Induction of Tumor Antigen-Specific Immunotherapeutic Response. Mol Imaging Biol 22, 549–561 (2020). https://doi.org/10.1007/s11307-019-01393-8
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DOI: https://doi.org/10.1007/s11307-019-01393-8