Abstract
Background aims. 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 19F 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 19F 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.
Acknowledgments/disclosure of interests
The authors thank Vinod Kaimal and Patrick McConville from MIR, and Lisa Pusateri and Gayathri Withers from Carnegie Mellon University, for their technical assistance. We also thank Charlie O'Hanlon for logistical help and critical comments. The authors BMH, AB, ADN and RBM are employed by Celsense Inc., the supplier of the 19F MRI tracer agent used in this study. This work was supported in part by the National Institutes of Health (SBIR RAI078602A and R01 CA134633).