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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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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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Authors and Affiliations

  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

    Corby Fink, Michael Smith & Gregory A. Dekaban

  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

    Jeffrey M. Gaudet, Ashley Makela & Paula J. Foster

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  1. Corby Fink
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  2. Michael Smith
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Correspondence to Gregory A. Dekaban.

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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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