The effect of irradiation on the biodistribution of radiolabeled pegylated liposomes

The effect of irradiation on the biodistribution of radiolabeled pegylated liposomes
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DOI:
10.1016/s0360-3016(01)01508-5
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发表时间:
2001-07-01
影响因子:
7
通讯作者:
Stewart, JSW
Stewart, JSW
中科院分区:
医学1区
文献类型:
--
作者:
Harrington, KJ;Rowlinson-Busza, G;Stewart, JSW

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目的:作为开发靶向脂质体放射增敏剂的一部分,研究了全身照射(TBI)对荷瘤裸鼠体内in -111- dtpa标记的聚乙二醇脂质体(IT)LPL的生物分布和药代动力学的影响。方法和材料:小鼠接受TBI (2 Gy或5 Gy),根据两种方案:(1)检测注射脂质体前30 min照射对96 h内IDLPL在肿瘤和正常组织生物分布时间的影响;(2)为检测注射脂质体前72 h ~ 1 h辐射对24 h肿瘤和正常组织对IDLPL摄取的影响,在gamma计数仪上通过解剖和定量测量肿瘤和组织/器官对脂质体的摄取水平。对于大多数组织(肿瘤、肝、肾、肺、皮肤、心脏和中枢神经系统),照射没有改变IDLPL的生物分布,TBI似乎增加了脾摄取,但进一步的分析显示,这种影响是由于照射小鼠脾脏重量减少所致。辐照小鼠的小肠、胃、肌肉骨骼系统、雌性生殖道和肾上腺对IDLPL的摄取增加。结论:这些结果表明,在根治性放疗期间同时使用脂质体放射增敏剂可能是安全的。然而,在大量小肠或造血组织将被照射的情况下,应谨慎行事。(C) 2001爱思唯尔科学公司
Purpose: The effect of total-body irradiation (TBI) on the biodistribution and pharmacokinetics of In-111-DTPA-labeled pegylated liposomes (IT)LPL) was evaluated in tumor-bearing nude mice as part of an ongoing effort to develop liposome-targeted radiosensitizers, Methods and Materials: Mice received TBI (2 Gy or 5 Gy) according to two protocols: (1) to test the effect of radiation delivered 30 min before liposome injection on the time course of IDLPL biodistribution to tumor and normal tissues over 96 h; (2) to test the effect of radiation at times ranging from 72 h to 1 h before liposome injection on tumor and normal tissue uptake of IDLPL at 24 h, Tumor and tissue/organ levels of liposome uptake were measured by dissection and quantitation in a gamma counter, Results: For most tissues (tumor, liver, kidney, lung, skin, heart, and central nervous system), irradiation did not alter IDLPL biodistribution, Splenic uptake appeared to be increased by TBI, but further analysis revealed that this effect was due to reduced splenic weight in irradiated mice. IDLPL uptake was increased in the small intestine, stomach, musculoskeletal system, female reproductive tract, and adrenal glands in irradiated mice. Conclusion: These findings suggest that concomitant administration of liposomal radiosensitizers during radical radiotherapy is likely to be safe. However, caution should be exercised in situations in which significant volumes of small intestine or hemopoietic tissue will be irradiated. (C) 2001 Elsevier Science Inc.