Quantification and characterization of granulocyte macrophage colony-stimulating factor activated human peripheral blood mononuclear cells by fluorine-19 cellular MRI in an immunocompromised mouse model - 21/08/20

Doi : 10.1016/j.diii.2020.02.004

C. Fink ^a,^c, M. Smith ^a,^c, O.C. Sehl ^b,^d, J.M. Gaudet ^b,^d,^{^{1
Present address: Magnetic Insight, Inc., Alameda, California 94501, USA.}}, T.C. Meagher ^f,^{^{2
Present address: Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.}}, N.A. Sheikh ^f, J.D. Dikeakos ^c, M.J. Rieder ^a,^e, P.J. Foster ^b,^d, G.A. Dekaban ^a,^c,^⁎
^a Biotherapeutics Research Laboratory, Robarts Research Institute, London, Ontario N6A 5B7, Canada
^b Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A 5B7, Canada
^c Department of Microbiology and Immunology, University of Western Ontario, London, Ontario N6A 5B7, Canada
^d Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5B7, Canada
^e Department of Pediatrics, University of Western Ontario, London, Ontario N6A 5B7, Canada
^f Dendreon Corporation, Seattle, Washington 98102, USA

^⁎Corresponding author. Robarts Research Institute, 1151 Richmond Street North, London, Ontario, N6A 5B7, Canada.Robarts Research Institute1151 Richmond Street NorthLondon, OntarioN6A 5B7Canada

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Highlights

•	Cell-based immunotherapies are an emerging pillar of cancer therapy.
•	Perfluorocarbon labeling and in vivo MRI tracking of therapeutic cells is feasible.
•	In vivo real-time imaging of therapeutic cells to predict immunotherapeutic outcome.
•	Cellular MRI is applicable across therapeutic cell types and disease states.

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Abstract

Purpose

The purpose of this study was to test fluorine-19 (19F) cellular magnetic resonance (MRI) as a non-invasive imaging modality to track therapeutic cell migration as a surrogate marker of immunotherapeutic effectiveness.

Materials and methods

Human peripheral blood mononuclear cell- (PBMC)-derived antigen presenting cell (APC) were labeled with a 19F-perfluorocarbon (PFC) and/or activated with granulocyte macrophage colony-stimulating factor (GM-CSF). Viability, phenotype and cell lineage characterization preceded 19F cellular MRI of PFC⁺ PBMC under both pre-clinical 9.4 Tesla (T) and clinical 3T conditions in a mouse model.

Results

A high proportion of PBMC incorporated PFC without affecting viability, phenotype or cell lineage composition. PFC⁺ PBMC were in vivo migration-competent to draining and downstream lymph nodes. GM-CSF addition to culture increased PBMC migration to, and persistence within, secondary lymphoid organs.

Conclusion

19F cellular MRI is a non-invasive imaging technique capable of detecting and quantifying in vivo cell migration in conjunction with an established APC-based immunotherapy model. 19F cellular MRI can function as a surrogate marker for assessing and improving upon the therapeutic benefit that this immunotherapy provides.

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Keywords : Antigen presenting cell (APC), Fluorine-19 (19F), Cellular magnetic resonance imaging (MRI), Cancer immunotherapy

Esquema

Introduction

Materials and methods

Animal care

Participants

PBMC isolation and PFC labeling

PBMC viability

Flow cytometry

Adoptive transfer of PBMC

MRI and quantification of PFC⁺ PBMC migration

Post-MRI verification of in vivo 19F signal

Statistical analysis

Results

GM-CSF promotes APC activation phenotype without affecting viability or PFC loading

GM-CSF promotes in vivo migration of PFC⁺ PBMC

Characterization of pLN migration-competent PFC⁺ PBMC

Detection of GM-CSF-treated PFC⁺ PBMC in vivo migration with a 3T clinical MRI set-up

Discussion

Prior PFC labeling does not interfere with GM-CSF-mediated APC activation

19F MRI detection and quantification of PFC⁺ PBMC in vivo migration at 9.4T

Characterization of pLN-migrated PFC⁺ cells

Cryopreserved PFC⁺ PBMC are lymph node migration-competent and detectable using a clinical 3T 19F MRI configuration

Conclusion

Human and animal rights

Informed consent and patient details

Disclosure of interest

Funding

Authors’ contributions

Exportación

Vol 101 - N° 9

P. 577-588 - septembre 2020 Regresar al número

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Quantification and characterization of granulocyte macrophage colony-stimulating factor activated human peripheral blood mononuclear cells by fluorine-19 cellular MRI in an immunocompromised mouse model - 21/08/20

Highlights

Abstract

Purpose

Materials and methods

Results

Conclusion

Esquema

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