A novel 19F agent for detection and quantification of human dendritic cells using magnetic resonance imaging

Bonetto, Fernando Jose; Srinivas, Mangala; Heerschap, Arend; Mailliard, Robbie; Ahrens, Eric T.; Figdor, Carl G.; de Vries, Jolanda M.
Publication Year
Published version
Monitoring of cell therapeutics in vivo is of major importance to estimate its efficacy. Here, we present a novel intracellular label for 19F magnetic resonance imaging (MRI)-based cell tracking, which allows for noninvasive, longitudinal cell tracking without the use of radioisotopes. A key advantage of 19F MRI is that it allows for absolute quantification of cell numbers directly from the MRI data. The 19F label was tested in primary human monocyte-derived dendritic cells. These cells took up label effectively, resulting in a labeling of 1.7 6 0.1 3 1013 19F atoms per cell, with a viability of 80 6 6%, without the need for electroporation or transfection agents. This results in a minimum detection sensitivity of about 2,000 cells/voxel at 7 T, comparable with gadolinium-labeled cells. Comparison of the detection sensitivity of cells labeled with 19F, iron oxide and gadolinium over typical tissue background showed that unambiguous detection of the 19F-labeled cells was simpler than with the contrast agents. The effect of the 19F agent on cell function was minimal in the context of cell-based vaccines. From these data, we calculate that detection of 30,000 cells in vivo at 3 T with a reasonable signal to noise ratio for 19F images would require less than 30 min with a conventional fast spin echo sequence, given a coil similar to the one used in this study. This is well within acceptable limits for clinical studies, and thus, we conclude that 19F MRI for quantitative cell tracking in a clinical setting has great potential.
Fil: Bonetto, Fernando Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina. Radboud University. Nijmegen Medical Centre; Países Bajos
Fil: Srinivas, Mangala. Radboud University. Nijmegen Medical Centre; Países Bajos
Fil: Heerschap, Arend. Radboud University. Nijmegen Medical Centre; Países Bajos
Fil: Mailliard, Robbie. Celsense Inc.; Estados Unidos
Fil: Ahrens, Eric T.. Carnegie Mellon University; Estados Unidos
Fil: Figdor, Carl G.. Radboud University. Nijmegen Medical Centre; Países Bajos
Fil: de Vries, Jolanda M.. Radboud University. Nijmegen Medical Centre; Países Bajos
cell tracking
magnetic resonance imaging
dendritic cell vaccines
cell quantification
Física Atómica, Molecular y Química
Ciencias Físicas
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Restricted access
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Consejo Nacional de Investigaciones Científicas y Técnicas
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