[1]刘宇,邱峰,吕志祥,等.99m锝标记多西他赛脂质体的制备及其在兔体内的组织分布研究[J].第三军医大学学报,2016,38(21):2303-2308.
 Liu Yu,Qiu Feng,Lyu Zhixiang,et al.Preparation of technetium labeled docetaxel liposome and its distribution in rabbits[J].J Third Mil Med Univ,2016,38(21):2303-2308.
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99m锝标记多西他赛脂质体的制备及其在兔体内的组织分布研究(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
38卷
期数:
2016年第21期
页码:
2303-2308
栏目:
基础医学
出版日期:
2016-11-15

文章信息/Info

Title:
Preparation of technetium labeled docetaxel liposome and its distribution in rabbits
作者:
刘宇邱峰吕志祥兰作平张梨王杰余瑜
重庆医科大学:附属第一医院药学部,附属第一医院核医学科,药学院药物化学与生物材料研究室
Author(s):
Liu Yu Qiu Feng Lyu Zhixiang Lan Zuoping Zhang Li Wang Jie Yu Yu

Department of Pharmacy, Department of Nuclear Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016; Department of Pharmaceutical Chemistry and Biological Materials, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China

关键词:
多西他赛脂质体组织分布99mTC标记靶向参数
Keywords:
docetaxel liposome tissue distribution 99mTC labeling target parameter
分类号:
R817.9; R944.9; R969.1
文献标志码:
A
摘要:

目的     考察多西他赛脂质体(DTX-LP)在兔体内的生物分布及其在各主要脏器的靶向参数。方法       通过固体分散与泡腾组合技术,使用放射性同位素锝(99mTC)对DTX-LP进行标记(DTX-LP-99mTC)。考察DTX-LP-99mTC的外观、粒径、Zeta电荷、包封率、载药量以及放射化学纯度及稳定性。将DTX-LP-99mTC或游离锝(99mTC-Free)经耳缘静脉注射入兔体内,经SPECT/CT静态采集数据及计算机融合显像获得DTX-LP-99mTC及99mTC-Free在兔体内的放射性影像。另将注射DTX-LP-99mTC或99mTC-Free的兔分别于给药后1、2、4、8、12 h处死,使用甲状腺功能测定仪采集兔各离体器官的放射性计数,并计算各脏器的相对摄取率(Re)和靶向效率(Te)。结果      DTX-LP-99mTC平均粒径为726 nm,Zeta电荷为-35.6 mV,包封率及载药量分别为(90.27±1.15)%和(1.30±0.20)%。在室温放置或兔血清中37 ℃温育1、4、12 h后,DTX-LP-99mTC的放射化学纯度分别为98.45%、96.32%、94.28%及96.78%、93.45%、91.56%。放射性影像显示DTX-LP-99mTC在兔肺浓聚;每克兔组织的放射性计数由高到低排列,在DTX-LP-99mTC组为肺、脾、肝、肾、心、脑,在99mTC-Free组为肝、脾、肾、心、肺、脑,同一时间点相同脏器的放射性计数在两组之间差异有统计学意义(P<0.01)。Re值表明,DTX-LP99mTC组在肺、脾和脑的放射性计数分别是99mTC-Free组的64.41、1.62倍和1.57倍,而心、肝、肾的放射性计数较99mTC-Free组明显减少。Te值表明,DTX-LP-99mTC在兔肺的放射性计数是脑的64.01倍,心的40.73倍,肾的14.01倍,肝的3.22倍。结论      DTX-LP主要浓集在兔肺,具有高度的肺靶向性。
 

Abstract:

Objective      To investigate the tissue distribution of docetaxel liposome (DTX-LP) in rabbits. Methods     DTX-LP was labeled with 99mTC (DTX-LP-99mTC) by solid dispersion and effervescent techniques. The appearance,  particle size, Zeta potential, encapsulation efficiency, drug loading rate and radiochemical purity of DTX-LP-99mTC were investigated. DTX-LP-99mTC or 99mTC-Free was injected to rabbits through ear vein, respectively. Then the rabbits were scanned with SPECT/CT to obtain the three-dimensional radioactive images. The rabbits were sacrificed at 1, 2, 4, 8 and 12 h after injection, and the heart, liver, spleen, lungs, kidneys and brain were harvested. The radioactive counts (RC) of these organs were detected using thyroid function tester. According to RC, the average relative uptake rate (Re) and average targeting efficiency (Te) of each organ were calculated. ResultsDTX-LP-99mTC was in spherical shape, at a particle size of 726 nm and with a Zeta potential of -35.6 mV. Its encapsulation efficiency and drug loading rate were (90.27±1.15)% and (1.30±0.20)%, respectively. After placing at room temperature for 1, 4 and 12 h, the radiochemical purity of DTX-LP-99mTC was 98.45%, 96.32% and 94.28%, respectively, while it was 96.78%, 93.45% and 91.56% separately after being incubated at 37 ℃ in rabbit serum. The radioactive enriched image of lung was observed in the rabbits injected with DTX-LP-99mTC. RC of per gram tissue in the DTX-LP-99mTC group was reduced in the lungs, spleen, liver, kidneys, heart and brain in order. In contrast, it was in the liver, spleen, kidneys, heart, lungs and brain in the 99mTC-Free group. At the same time, RC of the same organ were significant different between DTX-LP-99mTC group and 99mTC-free group (P<0.01). Re showed that the RC of the lungs, spleen and brain were by 64.41, 1.62 and 1.57 times higher in the DTX-LP-99mTC group than the 99mTC-Free group, respectively. But the RC of the heart, liver and kidneys in DTX-LP-99mTC group were significantly lower than that of 99mTC-Free group. In the DTX-LP-99mTC group, the RC of lung was 64.01 times higher than that of the brain, 40.73 times higher than that of the heart, 14.01 times than that of the kidneys and 3.22 times than that of the liver, respectively. Conclusion     DTX-LP is accumulated in the rabbit’s lungs, showing excellent lung-targeting effect.

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更新日期/Last Update: 2016-11-09