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