Functional assessment of human dendritic cells labeled for in vivo (19)F magnetic resonance imaging cell tracking.
OBJECTIVE
Dendritic cells (DC) are increasingly being used as cellular vaccines to treat cancer and infectious diseases. While there have been some promising results in early clinical trials using DC-based vaccines, the inability to visualize non-invasively the location, migration and fate of cells once adoptively transferred into patients is often cited as a limiting factor in the advancement of these therapies. A novel perflouropolyether (PFPE) tracer agent was used to label human DC ex vivo for the purpose of tracking the cells in vivo by (19)F magnetic resonance imaging (MRI). We provide an assessment of this technology and examine its impact on the health and function of the DC.


METHODS
Monocyte-derived DC were labeled with PFPE and then assessed. Cell viability was determined by examining cell membrane integrity and mitochondrial lipid content. Immunostaining and flow cytometry were used to measure surface antigen expression of DC maturation markers. Functional tests included bioassays for interleukin (IL)-12p70 production, T-cell stimulatory function and chemotaxis. MRI efficacy was demonstrated by inoculation of PFPE-labeled human DC into NOD-SCID mice.


RESULTS
DC were effectively labeled with PFPE without significant impact on cell viability, phenotype or function. The PFPE-labeled DC were clearly detected in vivo by (19)F MRI, with mature DC being shown to migrate selectively towards draining lymph node regions within 18 h.


CONCLUSIONS
This study is the first application of PFPE cell labeling and MRI cell tracking using human immunotherapeutic cells. These techniques may have significant potential for tracking therapeutic cells in future clinical trials.
Helfer
Brooke M
BM
Department of Research and Development, Celsense Inc., Pittsburgh, Pennsylvania, USA.
Balducci
Anthony
A
Nelson
Aaron D
AD
Janjic
Jelena M
JM
Gil
Roberto R
RR
Kalinski
Pawel
P
de Vries
I Jolanda M
IJ
Ahrens
Eric T
ET
Mailliard
Robbie B
RB
D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002470:Cell Survival; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004655:Emulsions; D004986:Ether / Q000378:metabolism; D005461:Fluorine / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009000:Monocytes / Q000166:cytology; D010641:Phenotype; D013194:Staining and Labeling; D014183:Transplantation, Heterologous
D004655:Emulsions; D004986:Ether; D018664:Interleukin-12; D005461:Fluorine