Synthesis and preliminary evaluation of 99mTc-spermine as a tumor imaging agent
Synthesis and preliminary evaluation of 99mTc-spermine as a tumor imaging agent
复制标题
DOI：
10.1007/s10967-012-2082-6
复制
发表时间：
2012-08
影响因子：
1.6
通讯作者：
Yu Xu;Shi Luo;D. Pan;Li Wang;Ya Ru Zhou;Min Yang
中科院分区：
文献类型：
--
作者：
Yu Xu;Shi Luo;D. Pan;Li Wang;Ya Ru Zhou;Min Yang
多胺对于所有细胞的生长和生存至关重要，多胺的生物合成和运输在肿瘤中非常活跃。为了开发一种新的肿瘤显像剂，用99mTc标记内源性多胺精胺，并通过体外和体内研究评估其特性。 99mTc 标记的精胺探针（99mTc-spermine）通过直接预镀锡程序合成，并在 pH、反应时间、精胺和 SnCl2 的量方面优化了标记程序。还评估了 99mTc-精胺的稳定性及其积累到 4T1 肿瘤细胞中的能力。在 4T1 荷瘤小鼠中研究了 99mTc-精胺的生物分布。在最佳条件下，整个放射合成在 10 分钟内完成，衰变校正收率为 96.5 ± 1.3%，放射化学纯度 >95%。99mTc-精胺在 37 和 4 °C 下稳定至少 6 小时。体外测试表明，99mTc-精胺能够渗透到 4T1 肿瘤细胞中，过量的精胺会阻止该化合物在模型中的积累。生物分布研究显示，注射后 30 分钟肿瘤摄取量达到峰值，达到 1.82 ± 0.19% ID%/g。注射后 30 分钟、1、2 和 4 小时时，探针的肿瘤与肌肉摄取比率分别为 3.60 ± 0.51、4.48 ± 0.29、4.82 ± 0.18、5.64 ± 0.10。区块研究表明 99mTc-精胺通过多胺转运系统与肿瘤具有特异性结合。 99mTc-精胺是一种在肿瘤成像中很有前途的放射性药物。需要进一步研究来确定 99mTc-精胺在诊断中的可用性。
Polyamines are essential for the growth and survival of all cells with biosynthesis and transportation of polyamines being very active in tumors. With the aim of developing a new tumor imaging agent, the endogenous polyamine, spermine was labeled with 99mTc, and its characters were also evaluated via in vitro and in vivo studies. 99mTc-labeled spermine probe (99mTc-spermine) was synthesized by the direct pretinning procedure and the labeling procedure was optimized with regard to the pH, reaction time, amounts of spermine and SnCl2. The stability of the 99mTc-spermine and its capacity to accumulate into 4T1 tumor cells were also evaluated. Biodistribution of 99mTc-spermine was studied in 4T1 tumor-bearing mice. In the optimal conditions, the whole radiosynthesis was accomplished within 10 min with a decay-corrected yield of 96.5 ± 1.3 % and radiochemical purity of >95 %.99mTc-spermine was stable at both 37 and 4 °C for at least 6 h. In vitro tests revealed that the ability of 99mTc-spermine to penetrate in 4T1 tumour cells and an excess of spermine blocked the accumulation of the compound in the models. Biodistribution studies showed a high tumor uptake peaked at 30 min post-injection with 1.82 ± 0.19 % ID%/g. The tumor to muscle uptake ratios of the probe were 3.60 ± 0.51, 4.48 ± 0.29, 4.82 ± 0.18, 5.64 ± 0.10, respectively at 30 min, 1, 2 and 4 h postinjection. Block studies indicated that 99mTc-spermine had specific binding of tumor via polyamine transport systems. 99mTc-spermine is a promising radiopharmaceutical in tumor imaging. Further studies are required to determine the usability of 99mTc–spermine for diagnosis purposes.