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

Monitoring of cell therapeutics in vivo is of major importance to estimate its efficacy. Here, we present a novel intracellular label for F-19 magnetic resonance imaging (MRI)-based cell tracking, which allows for noninvasive, longitudinal cell tracking without the use of radioisotopes. A key advantage of F-19 MRI is that it allows for absolute quantification of cell numbers directly from the MRI data. The F-19 label was tested in primary human monocyte-derived dendritic cells. These cells took up label effectively, resulting in a labeling of 1.7 +/- 0.1 x 10(13) F-19 atoms per cell, with a viability of 80 +/- 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 F-19, iron oxide and gadolinium over typical tissue background showed that unambiguous detection of the F-19-labeled cells was simpler than with the contrast agents. The effect of the F-19 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 F-19 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 F-19 MRI for quantitative cell tracking in a clinical setting has great potential.