Ex vivo Cell Labeling with64Cu-Pyruvaldehyde-Bis (N4-Methylthiosemicarbazone) for Imaging Cell Trafficking in Mice with Positron-Emission Tomography

We have used copper-64-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (64Cu-PTSM) to radiolabel cells ex vivo for in vivo positron-emission tomography (PET) imaging studies of cell trafficking in mice and for eventual application in patients. 2-18F-Fluoro-2-deoxy-D-glucose (FDG) cell labeling also was evaluated for comparison.64Cu-PTSM uptake by C6 rat glioma (C6) cells increased for 180 min and then stabilized. The labeling efficiency was directly proportional to64Cu-PTSM concentration and influenced negatively by serum. Label uptake per cell was greater with64Cu-PTSM than with FDG. However, both64Cu-PTSM- and FDG-labeled cells showed efflux of cell activity into supernatant. The64Cu-PTSM labeling procedure did not interfere significantly with C6 cell viability and proliferation rate. MicroPET images of living mice indicate that tail-vein-injected labeled C6 cells traffic to the lungs and liver. In addition, transient splenic accumulation of radioactivity was clearly detectable in a mouse scanned at 3.33 h postinfusion of64Cu-PTSM-labeled lymphocytes. In contrast, the liver was the principal organ of tracer localization after tail-vein administration of64Cu-PTSM alone. These results indicate that in vivo imaging of cell trafficking is possible with64Cu-PTSM-labeled cells. Given the longer t1/2of64Cu (12.7 h) relative to18F (110 min), longer cell-tracking periods (up to 24-36 h) should be possible now with PET.