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 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 BajosFil: Srinivas, Mangala. Radboud University. Nijmegen Medical Centre; Países BajosFil: Heerschap, Arend. Radboud University. Nijmegen Medical Centre; Países BajosFil: Mailliard, Robbie. Celsense Inc.; Estados UnidosFil: Ahrens, Eric T.. Carnegie Mellon University; Estados UnidosFil: Figdor, Carl G.. Radboud University. Nijmegen Medical Centre; Países BajosFil: de Vries, Jolanda M.. Radboud University. Nijmegen Medical Centre; Países Bajo