Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography

We have used copper-64-pyruvaidehyde-bis(N-4-methylthiosemicarbazone) (Cu-64-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-[F-18]-Fluoro-2-deoxy-D-glucose (FDG) cell labeling also was evaluated for comparison. Cu-64-PTSM uptake by C6 rat glioma (U) cells increased for 180 min and then stabilized. The labeling efficiency was directly proportional to Cu-64-PTSM concentration and influenced negatively by serum. Label uptake per cell was greater with Cu-64-PTSM than with FDG. However, both Cu-64-PTSM- and FDG-labeled cells showed efflux of cell activity into supernatant. The Cu-64-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 of Cu-64-PTSM-labeled lymphocytes. In contrast, the liver was the principal organ of tracer localization after tail-vein administration of 64Cu-PTSM alone. These results indicate that in vivo imaging of cell trafficking is possible with Cu-64-PTSM-labeled cells. Given the longer t(1/2) of Cu-64 (12.7 h) relative to F-18 (110 min), longer cell-tracking periods (up to 24-36 h) should be possible now with PET.