^(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

Preparation of technetium labeled docetaxel liposome and its distribution in rabbits

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(^(99m)TC)对DTX-LP进行标记(DTXLP-^(99m)TC)。考察DTX-LP-^(99m)TC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-^(99m)TC或游离锝(^(99m)TC-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-^(99m)TC及^(99m)TC-Free在兔体内的放射性影像。另将注射DTX-LP-^(99m)TC或^(99m)TCFree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-^(99m)TC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-^(99m)TC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-^(99m)TC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-^(99m)TC组为肺、脾、肝、肾、心、脑,在^(99m)TC-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-^(99m)TC组在肺、脾和脑的放射性计数分别是^(99m)TC-Free组的64.41、1.62倍和1.57倍,而心、肝、肾的放射性计数较^(99m)TCFree组明显减少。Te值表明,DTX-LP-^(99m)TC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。

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. Results DTX-LP-^99mTC was in spherical shape,at a particlesize 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 was96. 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 DTXLP-^99mTC group than the^99mTC-Free group,respectively. But the RC of the heart,liver and kidneys in DTXLP-^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.