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

C Fink; M Smith; O C Sehl; J M Gaudet; T C Meagher; N A Sheikh; J D Dikeakos; M J Rieder; P J Foster; G A Dekaban

doi:10.1016/j.diii.2020.02.004

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

Diagn Interv Imaging. 2020 Sep;101(9):577-588. doi: 10.1016/j.diii.2020.02.004. Epub 2020 Feb 28.

Authors

C Fink¹, M Smith¹, O C Sehl², J M Gaudet², T C Meagher³, N A Sheikh³, J D Dikeakos⁴, M J Rieder⁵, P J Foster², G A Dekaban⁶

Affiliations

¹ Biotherapeutics Research Laboratory, Robarts Research Institute, London, Ontario N6A 5B7, Canada; Department of Microbiology and Immunology, University of Western Ontario, London, Ontario N6A 5B7, Canada.
² Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A 5B7, Canada; Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5B7, Canada.
³ Dendreon Corporation, Seattle, Washington 98102, USA.
⁴ Department of Microbiology and Immunology, University of Western Ontario, London, Ontario N6A 5B7, Canada.
⁵ Biotherapeutics Research Laboratory, Robarts Research Institute, London, Ontario N6A 5B7, Canada; Department of Pediatrics, University of Western Ontario, London, Ontario N6A 5B7, Canada.
⁶ Biotherapeutics Research Laboratory, Robarts Research Institute, London, Ontario N6A 5B7, Canada; Department of Microbiology and Immunology, University of Western Ontario, London, Ontario N6A 5B7, Canada. Electronic address: dekaban@robarts.ca.

PMID: 32122802
DOI: 10.1016/j.diii.2020.02.004

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.

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

MeSH terms

Animals
Fluorine
Granulocyte-Macrophage Colony-Stimulating Factor*
Granulocytes
Humans
Leukocytes, Mononuclear*
Macrophage Colony-Stimulating Factor
Magnetic Resonance Imaging
Mice

Substances

Fluorine
Macrophage Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor