Goins B, Klipper R, Rudolph A S, Phillips W T
Radiology Department, University of Texas Health Science Center at San Antonio 78284-7800.
J Nucl Med. 1994 Sep;35(9):1491-8.
In this study, liposomes labeled with 99mTc have been evaluated as tumor imaging agents.
Liposomes containing reduced glutathione and carrying either a negative surface charge or no surface charge were labeled with 99mTc using the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO). The 99mTc-liposomes were intravenously injected into the tail vein of nuce mice which had been implanted intramuscularly in the thigh with nontransfected Chinese hamster ovary cells. Gamma camera images were acquired at 1, 4 and 22 hr and compared with tissue biodistribution studies at 24 hr postinjection.
Tumors could be distinguished from normal thigh muscle at 4 hr postinjection for both formulations. Tumor-to-muscle ratios were not significantly different for the two formulations due to the increased normal muscle activity at 24 hr for the neutral liposomes. Liver-to-tumor, liver-to-blood, spleen-to-tumor and spleen-to-blood ratios were significantly lower for the neutral 99mTc-liposomes than for the negative 99mTc-liposomes. Neutral 99mTc-liposomes were cleared slower by the reticuloendothelial system, and therefore remained in the circulation for a longer period of time.
The results of this study indicate that both formulations could be used as tumor imaging agents, but that neutral 99mTc-liposomes would be more suitable as a drug delivery agent due to their increased total uptake by the tumor and decreased nonspecific uptake by the reticuloendothelial system.
在本研究中,已对用99mTc标记的脂质体作为肿瘤成像剂进行了评估。
使用亲脂性螯合剂六甲基丙烯胺肟(HMPAO),将含有还原型谷胱甘肽且表面带负电荷或不带表面电荷的脂质体用99mTc标记。将99mTc标记的脂质体静脉注射到裸鼠的尾静脉中,这些裸鼠的大腿肌肉中已肌肉注射了未转染的中国仓鼠卵巢细胞。在注射后1、4和22小时采集γ相机图像,并与注射后24小时的组织生物分布研究进行比较。
两种制剂在注射后4小时均可将肿瘤与正常大腿肌肉区分开来。由于中性脂质体在24小时时正常肌肉活性增加,两种制剂的肿瘤与肌肉比值无显著差异。中性99mTc标记的脂质体的肝与肿瘤、肝与血液、脾与肿瘤以及脾与血液的比值明显低于阴性99mTc标记的脂质体。中性99mTc标记的脂质体被网状内皮系统清除较慢,因此在循环中停留的时间更长。
本研究结果表明,两种制剂均可作为肿瘤成像剂,但中性99mTc标记的脂质体由于其肿瘤总摄取量增加且网状内皮系统非特异性摄取减少,更适合作为药物递送剂。