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Molecular Imaging and Biology

Erschienen in:

08.07.2019 | Research Article

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

verfasst von: Corby Fink, Michael Smith, Jeffrey M. Gaudet, Ashley Makela, Paula J. Foster, Gregory A. Dekaban

Erschienen in: Molecular Imaging and Biology | Ausgabe 3/2020

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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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Titel: Fluorine-19 Cellular MRI Detection of In Vivo Dendritic Cell Migration and Subsequent Induction of Tumor Antigen-Specific Immunotherapeutic Response
verfasst von: Corby Fink
Michael Smith
Jeffrey M. Gaudet
Ashley Makela
Paula J. Foster
Gregory A. Dekaban
Publikationsdatum: 08.07.2019
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 3/2020
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-019-01393-8

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

Abstract

Purpose

Procedures

Results

Conclusions

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Abstract

Purpose

Procedures

Results

Conclusions

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