title: Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography.
abstract: 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 to 64Cu-PTSM concentration and influenced negatively by serum. Label uptake per cell was greater with 64Cu-PTSM than with FDG. However, both 64Cu-PTSM- and FDG-labeled cells showed efflux of cell activity into supernatant. The 64Cu-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 64Cu-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 64Cu-PTSM-labeled cells. Given the longer t(1/2) of 64Cu (12.7 h) relative to 18F (110 min), longer cell-tracking periods (up to 24-36 h) should be possible now with PET.
authors.affiliation: The Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, CA 90095-1770, USA.
authors.forename: Nona
authors.initials: N
authors.lastname: Adonai
authors.forename: Nora
authors.initials: N
authors.lastname: Adonai
authors.forename: Khoi N
authors.initials: KN
authors.lastname: Nguyen
authors.forename: Joseph
authors.initials: J
authors.lastname: Walsh
authors.forename: M
authors.initials: M
authors.lastname: Iyer
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toyokuni
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: Timothy
authors.initials: T
authors.lastname: McCarthy
authors.forename: Deborah W
authors.initials: DW
authors.lastname: McCarthy
authors.forename: Sanjiv Sam
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D003301:Copper Radioisotopes; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005910:Glioma; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D013882:Thiosemicarbazones / Q000378:metabolism / Q000633:toxicity; D014055:Tomography, Emission-Computed / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D019788:Fluorodeoxyglucose F18; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex