Adonai Nona, Adonai Nora, Nguyen Khoi N, Walsh Joseph, Iyer M, Toyokuni Tatsushi, Phelps Michael E, McCarthy Timothy, McCarthy Deborah W, Gambhir Sanjiv Sam
The Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, CA 90095-1770, USA.
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3030-5. doi: 10.1073/pnas.052709599. Epub 2002 Feb 26.
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.
我们已使用铜-64-丙酮醛双（N4-甲基硫代半卡巴腙）（64Cu-PTSM）对细胞进行离体放射性标记，用于小鼠体内细胞转运的正电子发射断层扫描（PET）成像研究，并最终应用于患者。还评估了2-[18F]-氟-2-脱氧-D-葡萄糖（FDG）细胞标记以作比较。C6大鼠胶质瘤（C6）细胞对64Cu-PTSM的摄取在180分钟内增加，然后稳定下来。标记效率与64Cu-PTSM浓度成正比，并受到血清的负面影响。每个细胞对64Cu-PTSM的摄取量大于对FDG的摄取量。然而，64Cu-PTSM标记的细胞和FDG标记的细胞均显示细胞活性外流到上清液中。64Cu-PTSM标记程序对C6细胞活力和增殖率没有明显干扰。活体小鼠的微型PET图像表明，经尾静脉注射标记的C6细胞会转移至肺和肝脏。此外，在输注64Cu-PTSM标记的淋巴细胞后3.33小时扫描的一只小鼠中，明显可检测到脾脏有短暂的放射性聚集。相比之下，单独经尾静脉给予64Cu-PTSM后，肝脏是示踪剂定位的主要器官。这些结果表明，用64Cu-PTSM标记的细胞进行细胞转运的体内成像具有可行性。鉴于64Cu的半衰期（12.7小时）比18F（110分钟）长，现在使用PET应该可以实现更长的细胞追踪期（长达24 - 36小时）。
