19F-MRI for tracking NK Cells after adoptive transfer (CAM1P.240)

Abstract

Abstract Natural killer (NK) cells have shown anti-tumor responses against solid tumors. However, it is not known if NK cells traffic directly to tumors and mediate their cytotoxicity, or if they indirectly mediate their anti-tumor effects by stimulating other effector cells. Current methods of tracking immune cells by imaging of 1H contrast agents, such as iron oxide particles, are not ideal as a large part of the 1H signal comes from water in the tissues. Because there are trace amounts of fluorine in the body, we have optimized the non-radioactive isotope 19-fluorine (19F) as a means of tracking human NK cells by magnetic resonance imaging (MRI). In vitro, we show that NK cell viability, their ability to secrete granzyme B or IFN-γ and cytotoxicity against K562 leukemia cells are not affected by 19F labeling and are similar to unlabeled cells. There was also no impact on expression of natural cytotoxicity receptors, NKG2D or DNAM-1. MR Spectroscopy has shown that NK cells highly take up 19F, with up to 10^12 atoms/cell. In vivo, 19F-labeled NK cells injected in the footpad of NOD-SCID-gamma (c)-/- mice were nontoxic and detectable by MRI. Overall, perfluorcarbon 19F labeling of NK cells represents a successful method to track and quantify the number of apparent cells in a region of interest without altering their cytotoxic function. Importantly, 19F imaging will enable us to monitor NK cells after their infusion allowing us to determine how they induce their anti-tumor effects.