^(99)Tc^m与^(18)F标记DG Spca-1细胞系体外实验研究

Experimental study of ^(99)Tc^mO(DGDTC)_2 and ^(18)F on pulmonary adenocarcinoma cell Spca-1

目的探讨在肺癌葡萄糖代谢方面,新型葡萄糖代谢显像剂99 Tcm标记的葡萄糖氨荒酸盐配合物99 TcmO(DGDTC)2单光子发射计算机断层摄影术(single photon emission computed tomography,SPECT)显像替代18F-氟脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)正电子发射断层扫描(positron emission tomography,PET)显像的可行性。方法通过配体交换反应,制备99 TcmO(DGDTC)2配合物,HPLC分析法检测99 TcmO(DGDTC)2的放化纯。常规孵育Spca-1细胞备用。在分别加入99 TcmO(DGDTC)2和18F-FDG后,99 TcmO(DGDTC)2组分别于30min、1h、2h、3h和4h5个时间点测定Spca-1细胞内外放射性计数,18F-FDG组分别于10、20、30、60和120min 5个时间点测定Spca-1细胞内外的放射性计数,计算摄取率及细胞各个时间点的Cin/Cout值。结果成功制备了99 TcmO(DGDTC)2配合物。HPLC分析法测定99 TcmO(DGDTC)2放射性化学纯度≥95%。注入99 TcmO(DGDTC)2后30min时间点百分注射剂量率(injection dose rate,ID)为(0.26±0.02)%,1h为(0.60±0.05)%,2h为(0.68±0.04)%,3h为(0.85±0.05)%,4h为(1.0±0.13)%;Cin/Cout30min为1.0,1h为2.0,2h为2.9,3h为1.7,4h为0.6。随时间延长,Spca-1细胞摄取99 TcmO(DGDTC)2逐渐增加,2h时达到摄取最大比值,3和4h逐渐下降。注入18 F-FDG后10 min个时间点ID为(0.40±0.05)%,20min为(0.72±0.02)%,30min为(0.95±0.03)%,60min为(1.03±0.05)%,120min为(1.16±0.13)%;Cin/Cout10min为1.2,20 min为2.0,30 min为4.2,60 min为3.5,120 min为3.0。随时间延长,Spca-1细胞摄取18F-FDG逐渐增加,30min时达到摄取最大比值,2h时开始下降。结论 99 TcmO(DGDTC)2制备后放射稳定性较好,肺癌Spca-1细胞能较好地摄取99 TcmO(DGDTC)2,摄取规律与摄取18 F-FDG显像剂的规律相似。99 TcmO(DGDTC)2SPECT显像有望成为替代18F-FDG PET显像的葡萄糖代谢显像剂。

OBJECTIVE To study the uptake of ^99Tc^m labeled glucose dithiocarbamate composition ^99 Tc^mO（DG- DTC）2 ] in pulmonary adenocarcinoma cell line Spca-1 by analyzing the in vitro results of tb.is new tracer and to observe the application value of Single-Photon Emission Computed Tomography with ^99Tc^m O（DGDTC）2 on lung cancer. The prob- ability of substitution for Positron emission tomography with 18 F-fluorodeoxyglucose was investigated. METHODS The complex 99 Tcm O（DGDTC）2 was prepared by ligand exchange action. HPLC was adopted to measure its radionuelidic purity. Spca-1 cells were incubated in conventional for use. There were two groups：in the first group,99 TcmO（DGDTC）2 was added, and in the second group,^18F-FDG was added into the cell plates. In the first group the uptake of the tracer was observed over 30 rain, 1 h, 2 h, 3 h and 4 h respectively after phosphate buffered solution was added. In the second group, the uptake of the tracer was observed over 10 min,20 min,30 min,60 min,120 rain respectively after phosphate buffered solution was added, then cells were collected and the radioactive uptake of the above two tracers in pulmonary adenocarcinoma cell line were measured by a y-ray spectrometer respectively. RESULTS The 99TemO（DGDTC）2 complex： the 99TcmO （DGDTC）2 complexes were successfully prepared and the radionuclidic purity of ^99Tc^mO （DGDTC）2 was ≥ 95% by method of HPLC. In vitro experiment as shown in the cells,the radio uptake of ^99Tc^m O（DGDTC） 2 increased gradually over time,the injection dose rates were （0.26±0.02）%,（0.60±0.05）%,（0.68±0.04）%,（0.85±0.05）% and （1.0±0.13）% for 30 min,1 h,2 h,3 h and 4 h respectively. The uptake of the tracer by Spea-1 cells reached the maximum in two hour （Cin/Cont was 2.9）, and then gradually decreased after 3 or 4 hours. Compared with the 99TcmO（DGDTC）2 group, the 18 F-FDG group the uptake of the tracer also showed a gradual increase over time, the uptake of the tracer by Spca-1 cells reached the maximum at 30 min post-administration （Cin/Cont was 4.2） ,and then decreased gradually after 2 hours. CONCLUSIONS The new tracer 99 Tcm labeled glucose dithiocarbamate composition [99 TcmO（DGDTC）z ] can be prepared with good radio stability. The experimental study in vitro showed the high uptake of ^99Tc^mO（DGDTC）2 in pulmonary adenoearcinoma cell line Spca-1. It has the similar regularity of the uptake of the tracer with the ^18F-FDG＇s. This study implicates the potential application value of 99 TcmO（DGDTC）2 in the imaging diagnosis of lung adenocarcinoma.