[1]杨明福,刘广元,李前伟.99Tcm-MAG3-K237的制备及其在健康动物体内的药代动力学和分布研究[J].第三军医大学学报,2010,32(05):482-485.
 Yang Mingfu,Liu Guangyuan,Li Qianwei.Preparation of 99Tcm-MAG3-K237 and its pharmacokinetics and distribution in health animals[J].J Third Mil Med Univ,2010,32(05):482-485.
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99Tcm-MAG3-K237的制备及其在健康动物体内的药代动力学和分布研究(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
32卷
期数:
2010年第05期
页码:
482-485
栏目:
论著
出版日期:
2010-03-15

文章信息/Info

Title:
Preparation of 99Tcm-MAG3-K237 and its pharmacokinetics and distribution in health animals
作者:
杨明福刘广元李前伟
第三军医大学西南医院核医学科
Author(s):
Yang Mingfu Liu Guangyuan Li Qianwei
Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
关键词:
血管生成抑制剂血管内皮生长因子受体2药代动力学放射性核素显像K237组织分布小鼠
Keywords:
angiogenesis inhibitors  vascular endothelial growth factor receptor-2 pharmacokinetics radionuclide imaging K237 tissue distribution rabbits mice
分类号:
R914.2;R817.1;R969.1
文献标志码:
A
摘要:
目的  探讨99Tcm标记血管内皮生长因子受体2(vascular endothelial growth factor receptor-2,VEGFR-2,KDR)小分子拮抗肽K237的方法,研究标记物在健康动物体内的药代动力学特性及体内分布特点。  方法   化学方法合成制备MAG3-K237,并用99Tcm标记;鉴定标记物的理化性质;测定标记物经新西兰大白兔静脉注射后不同时相血液放射性浓度,得出最佳房室模型与药代动力学参数;分别测定经尾静脉注射7.4 MBq标记物后的昆明小鼠各器官质量和放射性计数,经参考源校正后计算各脏器每克组织百分注射剂量率(%ID/g);经耳缘静脉注射37 MBq标记物,在SPECT下观察其在兔体内的动态分布。  结果  99Tcm-MAG3-K237的放化纯度为(97.98±0.76)%,比活度为(3.54±0.03) TBq/mmol;室温(25 ℃)下保存8 h后放化纯度为(96.15±0.37)%;半胱氨酸置换率为0.2%~0.37%;不与血清蛋白结合;兔体内动力学过程符合权重为1/c2的三室模型,快分布相半衰期(t1/2α)、慢分布相半衰期(t1/2β)及消除相半衰期(t1/2γ)分别为(4.00±3.53)、(24.48±9.84)、(852.24±444.00) min,清除率(CL)为(1.833±0.408) ml/min;标记物在健康小鼠体内清除迅速,肾脏、肝脏及肠道分布较多,但肝脏30 min后分布很少。   结论  本研究制备的99Tcm-MAG3-K237的放射化学纯度高,体内外稳定性好,血液清除速度快,通过肾脏和肝脏双重途径代谢。
Abstract:
Objective  To explore how to label small molecule inhibitor K237 (HTMYYHHYQHHL) of vascular endothelial growth factor receptor-2 (VEGFR-2, KDR) with technetium 99m and to study pharmacokinetic characteristics and body distribution of the labeled peptide in healthy animals.   Methods  MAG3-K237 was prepared through chemosynthesis, and then labeled it with 99Tcm. Then its stability and physicochemical properties were determined by paper chromatography. The best compartment model and its pharmacokinetic parameters were obtained through determining blood radioactive concentrations at 1.5, 3, 5, 10, 30, 60, 90, 120, 240 and 480 min after injection of 37 MBq 99Tcm-MAG3-K237 into 6 rabbits. SPECT imaging was applied to investigate the dynamic distribution of the peptide in rabbits. After 7.4 MBq 99Tcm-MAG3-K237 injected into 35 healthy mice via caudal vein, the mice were sacrificed in 1, 5, 10, 30, 60, 120 and 240 min respectively after the injection (n=5 at each time point), and then their samples of blood, heart, lungs, liver, spleen, intestine, muscle, bone and brain were collected to measure the weight and radioactive counting of each organ after injection, and to calculate %ID/g of each organ.   Results  The radiochemical purity of 99Tcm-MAG3-K237 was (97.98±0.76)%, which was (96.15±0.37)% after 8 h being conserved under room temperature (25℃) and the cysteine replacement rate was from 0.2% to 0.37% and the labeled peptide could not combine with blood serum protein. Its dynamics in rabbits conformed to the three-compartment model with the weight of 1/c2, and the main parameter were as follows: t1/2α, t1/2β and t1/2γ were 4.00±3.53, 24.48±9.84  and 852.24±444.00 min respectively; CL was 1.833±0.408 ml/min. SPECT imaging and distribution test in mice showed that the peptide could be quickly cleared from blood in healthy animals and distributed more in the kidney, liver and intestine, but its distribution in the liver became fewer in 30 min after injection.   Conclusion  We obtained the 99Tcm labeled peptide with high radiochemical purity (>95%) and perfect stability, which could be quickly cleared from blood and excreted though liver and kidney.

参考文献/References:

杨明福,刘广元,李前伟. 99Tcm-MAG3-K237的制备及其在健康动物体内的药代动力学和分布研究[J]. 第三军医大学学报,2010,32(5):482-485.

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更新日期/Last Update: 2010-03-05