Fluorine-19 Cellular MRI Detection of In Vivo Dendritic Cell Migration and Subsequent Induction of Tumor Antigen-Specific Immunotherapeutic Response

Corby Fink; Michael Smith; Jeffrey M Gaudet; Ashley Makela; Paula J Foster; Gregory A Dekaban

doi:10.1007/s11307-019-01393-8

Fluorine-19 Cellular MRI Detection of In Vivo Dendritic Cell Migration and Subsequent Induction of Tumor Antigen-Specific Immunotherapeutic Response

Mol Imaging Biol. 2020 Jun;22(3):549-561. doi: 10.1007/s11307-019-01393-8.

Authors

Corby Fink¹, Michael Smith¹, Jeffrey M Gaudet², Ashley Makela², Paula J Foster², Gregory A Dekaban³

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.
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.
³ 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. dekaban@robarts.ca.

PMID: 31286351
DOI: 10.1007/s11307-019-01393-8

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.

Keywords: Cancer immunotherapy; Cellular magnetic resonance imaging (MRI); Dendritic cell (DC); Fluorine-19 (F-19).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Neoplasm / immunology*
Cell Movement / immunology*
Cell Tracking / methods
Cells, Cultured
Contrast Media / chemistry
Dendritic Cells / cytology
Dendritic Cells / immunology*
Disease Models, Animal
Fluorine-19 Magnetic Resonance Imaging / methods*
Immunotherapy / methods*
Melanoma, Experimental / diagnostic imaging
Melanoma, Experimental / immunology*
Melanoma, Experimental / pathology
Melanoma, Experimental / therapy
Mice
Mice, Inbred C57BL
Skin Neoplasms / diagnostic imaging
Skin Neoplasms / immunology*
Skin Neoplasms / pathology
Skin Neoplasms / therapy

Substances

Antigens, Neoplasm
Contrast Media