同位素 ›› 2012, Vol. 25 ›› Issue (2): 65-70.DOI: 10.7538/tws.2012.25.02.0065

• 放射性药物与标记化合物 •    下一篇

神经肽类似物DOTA-Substance P的177Lu标记及其生物分布

梁积新1，2;李洪玉1,2;向学琴1,2;罗洪义2;胡连生2;邓新荣1;陈阳3;庄玲3;罗志福1，2   

  1. 1.中国原子能科学研究院 同位素研究所，北京102413;2.原子高科股份有限公司, 北京102413;3. 核工业北京401医院 核医学科, 北京102413
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2012-05-20 发布日期:2012-05-20

Radiolabeling of DOTA-Substance P With 177Lu and Biodistribution of 177Lu-DOTA-Substance P

LIANG Ji-xin1,2;LI Hong-yu1,2;XIANG Xue-qin1,2;LUO Hong-yi2;HU Lian-sheng2;DENG Xin-rong1;CHEN Yang3;ZHUANG Ling3;LUO Zhi-fu1,2   

  1. 1. Department of Isotopes, China Institute of Atomic Energy, Beijing 102413, China;2. HTA Co., LTD. , Beijjing 102413, China; 3. Department of Nuclear Medicine， Beijing 401 Hospital, China National Nuclear Corporation， Beijing 102413, China
  • Received:1900-01-01 Revised:1900-01-01 Online:2012-05-20 Published:2012-05-20

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摘要： 为探讨神经肽类药物177Lu-DOTA-Substance P（以下简称为177Lu-DOTA-SP）用于人胰腺癌PANC-1的肿瘤显像及治疗的可能性，研究了DOTA-SP的177Lu标记；考察了177Lu-DOTA-SP在室温下生理盐水中与在37 ℃小牛血清中的稳定性；评价了177Lu-DOTA-SP在正常昆明小鼠与人胰腺癌PANC-1模型裸鼠体内的生物分布特点，并对人胰腺癌PANC-1模型裸鼠进行了SPECT显像研究。结果表明，在优化条件下，DOTA-SP的177Lu标记率＞90%，纯化后，177Lu-DOTA-SP的放化纯度＞98%。177Lu-DOTA-SP在生理盐水与5%小牛血清中显示了良好的稳定性，与浓度较高的血清（10%）竞争反应时，其降解稍快。177Lu-DOTA-SP在正常昆明小白鼠体内的生物分布特点为：血清除快，肾放射性摄取高且滞留时间长；骨中有一定放射性摄取，且滞留长。177Lu-DOTA-SP在人胰腺癌PANC-1模型裸鼠中的体内分布结果表明，肿瘤细胞中放射性摄取在给药后不同时间点均高于正常胰腺细胞中的放射性摄取，提示在PANC-1肿瘤细胞中有NK-1受体存在。SPECT显像结果显示，177Lu-DOTA-SP在肿瘤细胞中放射性浓集并不明显。177Lu-DOTA-SP 应用于胰腺癌肿瘤显像与治疗的价值尚需进一步研究。

关键词: DOTA-Substance P, 177Lu标记, 生物分布

Abstract: The aim of this project is to evaluate the biodistribution of 177Lu-DOTA-SP in normal mice and in PANC-1 tumor bearing nude mice and to pave the way for its potentially medical application. In this study, 177Lu-DOTA-SP was successfully prepared with labeling yield of greater than 90% at optimized conditions and more than 98% of radiochemical purity after C18 Sep-Pak purification. 177Lu-DOTA-SP showed good stability in saline and in 5% serum while it decomposed slowly in 10% serum. Biodistribution studies in normal mice showed high uptake of 177Lu-DOTA-SP in the kidneys, indicating the excretion mainly by renal pathway. In addition, 177Lu-DOTA-SP was washed out from the blood quickly. Biodistribution of 177Lu-DOTA-SP in PANC-1 tumor bearing mice showed higher uptake in pancreatic tumor than that in normal pancreas, indicating the presence of NK-1 receptors in PANC-1 pancreatic tumor. However, from SPECT image, no radioactivity accumulation was observed in PANC-1 tumor. Further evaluation is needed to confirm its potential application for radiotherapy of pancreatic cancers.

Key words: DOTA-Substance P, 177Lu radiolabeling, biodistribution

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