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

Abstract

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 ± 0.1 × 1013 19F 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 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.

Selective In Vivo Visualization of Immune-Cell Infiltration in a Mouse Model of Autoimmune Myocarditis by Fluorine-19 Cardiac Magnetic Resonance

“…27 When PFCs were used for in vitro labeling experiments, no negative effects were found on cell viability and cell function of dendritic cells 28 and polymorphonuclear neutrophils. 29 In summary, these current and other preliminary results of 19 F MRI applications for inflammation detection and the fact that the PFCs exhibit a high safety profile, [27][28][29] suggest a feasible and highly desirable transition of this 19 F approach into a clinical application. From a biological point of view, future studies are needed to test whether human macrophages are able to incorporate PFC in vivo in sufficient quantities to allow for noninvasive detection by 19 F-CMR.…”

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

“…We, and others, have shown that the contrast generated by ironlabeled cells increases with the amount of iron/voxel but that this is only linear at low iron loadings; the change in contrast reaches a saturation plateau at higher iron loadings. 6,7 When quantifying the presence of iron-labeled stem cells over time, most studies measure the "signal void volume" 8,9 or the "number of black pixels", 10,11 and present the change relative to the first imaging time point.…”

19F-MRI for monitoring human NK cellsin vivo

“…25,26 Other investigators have also reported on the ability to ex vivo label other potential cell therapies with 19 F, including murine 30 and human neural stem cells, 31 human CD34 C hematopoietic stem cells (HSCs) and mouse bone marrow derived HSCs as well as murine 32 and human 33 19 F-MRI without apparent toxicity. 34 About 10 million DCs were injected intradermally into quadriceps and patients were imaged for about 9.5 min.…”