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

• Published in: Molecular imaging and biology Vol. 22; no. 3; pp. 549 - 561
• Main Authors: Fink, Corby, Smith, Michael, Gaudet, Jeffrey M., Makela, Ashley, Foster, Paula J., Dekaban, Gregory A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2020; Springer Nature B.V
• Subjects: Antigens; Bearing (direction); Bone marrow; Cancer; Cancer immunotherapy; Cell adhesion & migration; Cell culture; Cell migration; Dendritic cells; Fluorine; Imaging; Immune response; Immune system; Immunization; Immunotherapy; Magnetic resonance imaging; Medical imaging; Medicine; Medicine & Public Health; Melanoma; Microscopy; NMR; Nuclear magnetic resonance; Optimization; Osteoprogenitor cells; Perfluorocarbons; Phenotypes; Phenotyping; Radiology; Research Article; Tracking; Tumors; Viability; Dendritic cell (DC); Fluorine-19 (F-19); Cancer immunotherapy; Cellular magnetic resonance imaging (MRI)
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-019-01393-8

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 [ 19 F]perfluorocarbon ([ 19 F]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 [ 19 F]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.