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

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

Publication date: Jul 08, 2019

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.

Murine DC were generated from bone marrow precursors and labeled with a [F]perfluorocarbon ([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 [F]PFC (PFC)-labeled DC was first compared to control unlabeled DC by microscopy and then measured using F-19 cellular MRI.

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.

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.

Fink, C., Smith, M., Gaudet, J.M., Makela, A., Foster, P.J., and Dekaban, G.A. Fluorine-19 Cellular MRI Detection of In Vivo Dendritic Cell Migration and Subsequent Induction of Tumor Antigen-Specific Immunotherapeutic Response. 23311. 2019 Mol Imaging Biol.

Concepts Keywords
Antigen Magnetic resonance imaging
Bone Marrow B16 F10 tumor
Clinical Translation Immunization
Fluorine Immunotherapy
Immune Response Immunotherapies
Immunization Cryogenics
Immunotherapeutic Magnetic resonance imaging
Immunotherapies Celsense
Lymphoid Magnetic resonance imaging
Magnetic Resonance Imaging MRI
Magnitude
Melanoma
Modality
MRI
Optimization
Organ
Phenotype
Tumor
Vivo

Semantics

Type Source Name
pathway BSID Translation
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT F10
gene UNIPROT FAM110A
gene UNIPROT PCID2
gene UNIPROT CFP
gene UNIPROT SLC35G1
disease DOID cancer
disease MESH Tumor
gene UNIPROT CYREN

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