An Investigation of the Early Detection of Radiation Induced Apoptosis by 99mTc-Annexin V and 201Thallium-Chloride in a Lung Cancer Cell Line
An Investigation of the Early Detection of Radiation Induced Apoptosis by 99mTc-Annexin V and 201Thallium-Chloride in a Lung Cancer Cell Line
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DOI：
10.1269/jrr.11177
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发表时间：
2012-05-01
影响因子：
2
通讯作者：
Sawada, Satoshi
中科院分区：
文献类型：
--
作者：
Khoda, Mahbub E.;Utsunomiya, Keita;Sawada, Satoshi
本研究旨在探讨体外~(201)Tl(T1-201)和体内外~(99)Tc-HYNIC偶联Annexin V(TAV)在早期检测放射治疗(RT)疗效的替代指标--放射诱导的细胞凋亡中的作用。体外测定了5种不同剂量的伽玛射线照射后非小细胞肺癌的T1-201和TAV蓄积和外排。同时测定细胞株的复制速率(RR)。将相同的非小细胞肺癌细胞株接种于左侧股骨。体内无创T1-201和TAV示踪剂的生物分布研究。照射后48h，细胞RR随照射剂量的增加而降低。细胞凋亡数随照射剂量的增加而增加。9Gy组和12Gy组的T1-201累积量高于低照射组。在9Gy12Gy射线照射的细胞中观察到快速的T1-201外流。照射后48h，9Gy组和12Gy组Annexin V积聚高于对照组和3~6Gy组。在活体小鼠模型中证实，与未照射的对照组相比，在相对较高的9Gy射线照射下，移植瘤中的TAV摄取增加。TAV可能被证明是一种有效的放射性示踪剂，可通过细胞凋亡早期评估人类肺癌的放射治疗效果。
This study aims to investigate the efficacy of in vitro Thallium-201 Chloride (T1-201) and in vitro and in vivo Tc-99m HYNIC-coupled Annexin V (TAV) in the early detection of radiation induced apoptosis, a proxy indicator of radiation therapy (RT) efficacy. In vitro T1-201 and TAV accumulation and efflux in non-small cell lung cancer were measured post irradiation at 5 different gamma ray doses. The replication rates (RR) of the cell lines were also measured. The same non-small cell lung cancer line was inoculated into the left femur. In vivo non-invasive T1-201 and TAV tracer biodistribution studies were performed. Cell RR decrease with increased radiation dose was observed 48 hours after irradiation. Apoptotic cell number was found to have increased in response to 9 Gy and 12 Gy radiation dose. T1-201 accumulation in the 9 Gy and 12 Gy irradiation groups was found to be higher than the lower irradiation groups. Quick T1-201 efflux was observed in the 9 Gy and 12 Gy irradiated cells. At 48 hours after irradiation with 9 Gy and 12 Gy, Annexin V accumulation was found to be higher than in the control and 3-6 Gy groups. In vivo mouse model confirmed the increased TAV uptake in implanted tumors for relatively high 9 Gy irradiation as compared to non-irradiated controls. TAV may prove to be an effective radiotracer for early assessment of radiation therapy efficacy, via apoptosis, in human lung cancers.