Cay O, Kruskal J B, Nasser I, Thomas P, Clouse M E
Department of Radiological Sciences, Beth Israel Deaconess Medical Center, Boston MA, USA.
Radiology. 1997 Oct;205(1):95-101. doi: 10.1148/radiology.205.1.9314969.
To evaluate the intratumoral distribution of liposome-encapsulated doxorubicin.
Tumor-bearing livers of 24 mice were studied with in vivo fluorescence and electron microscopy after injection of liposomal doxorubicin in the hepatic artery, portal vein, or tail vein. Distribution and uptake of liposomes and doxorubicin in tumors were compared at 5, 30, and 60 minutes after injection. In vitro evaluation of uptake of doxorubicin in Kupffer cells and in human colorectal cancer cells incubated under normoxic and hypoxic conditions for 5, 30, and 60 minutes was performed with fluorescence microscopy.
Doxorubicin autofluorescence was seen in tumors 30 minutes after intraarterial and intraportal injection and was statistically significantly greater at 60 minutes (P < .001). Liposomes were observed in small tumors (diameter < 300 microns) and were trapped in Kupffer cells around larger, hypovascular tumors. Electron microscopy findings confirmed intracytoplasmic, perinuclear uptake of liposomes in tumor cells. In vitro, a higher proportion of doxorubicin was seen in cancer cells (92%) than in Kupffer cells (75%) after 60 minutes incubation.
Liposomal doxorubicin can be reliably delivered to liver metastases via the hepatic artery, eliminating need for tumor embolization. Further evaluation is warranted, and the drug may be useful for treating patients with unresectable liver metastases.
评估脂质体包裹阿霉素在肿瘤内的分布情况。
对24只荷瘤小鼠的肝脏进行研究，分别经肝动脉、门静脉或尾静脉注射脂质体阿霉素后，采用体内荧光和电子显微镜观察。在注射后5分钟、30分钟和60分钟，比较脂质体和阿霉素在肿瘤中的分布及摄取情况。采用荧光显微镜对在常氧和低氧条件下孵育5分钟、30分钟和60分钟的库普弗细胞及人结肠癌细胞摄取阿霉素的情况进行体外评估。
动脉内和门静脉内注射后30分钟肿瘤内可见阿霉素自发荧光，60分钟时在统计学上显著增强（P <.001）。在小肿瘤（直径<300微米）中观察到脂质体，且脂质体被困在较大的乏血管肿瘤周围的库普弗细胞中。电子显微镜检查结果证实肿瘤细胞内存在脂质体的胞质内核周摄取。体外实验中，孵育60分钟后，癌细胞中阿霉素的比例（92%）高于库普弗细胞（75%）。
脂质体阿霉素可通过肝动脉可靠地输送至肝转移灶，无需进行肿瘤栓塞。有必要进一步评估，该药物可能对治疗无法切除的肝转移患者有用。
