神经肽类似物DOTA-Substance P的^(177)Lu标记及其生物分布

Radiolabeling of DOTA-Substance P With ^(177)Lu and Biodistribution of ^(177)Lu-DOTA-Substance P

为探讨神经肽类药物177 Lu-DOTA-Substance P(以下简称为177 Lu-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177 Lu标记;考察了177 Lu-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177 Lu-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177 Lu标记率>90%,纯化后,177 Lu-DOTA-SP的放化纯度>98%。177 Lu-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。177 Lu-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。177 Lu-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,177 Lu-DOTA-SP在肿瘤细胞中放射性浓集并不明显。177 Lu-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。

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.