Oku N, Tokudome Y, Tsukada H, Okada S
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Biochim Biophys Acta. 1995 Aug 23;1238(1):86-90. doi: 10.1016/0005-2736(95)00106-d.
Long-circulating liposomes are known to accumulate passively in tumor tissues of tumor-bearing animals. To evaluate the in vivo behavior of such liposomes, we investigated the real-time liposomal trafficking by a non-invasive method using position emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, and palmityl-D-glucuronide (PGlcUA) in a molar ratio of 4:4:1 were prepared in the presence of 2-[18F]fluoro-2-deoxyglucose ([2-18F]FDG). [2-18F]FDG-labeled liposomes sized by extrusion through a filter with various-sized pores were administered to mice bearing Meth A sarcoma, and a PET scan was performed for 120 min. Small-sized, long-circulating liposomes (100 nm in diameter) constructed with PGlcUA tended to accumulate in the tumor tissues. On the contrary, control liposomes (100 nm in diameter) containing dipalmitoylphosphatidylglycerol instead of PGlcUA accumulated in the liver. Large-sized PGlcUA-containing liposomes (> 300 nm) also accumulated in the liver, as well as in the spleen. Time-activity curves indicated that the small long-circulating liposomes (< 200 nm) transiently accumulated in the liver right after the injection but that the accumulation there decreased time-dependently. These data suggest that, although the majority of small long-circulating liposomes remain in the bloodstream, some extravasate once into the interstitial spaces in the liver re-enter the bloodstream again, and finally accumulate in the tumor tissues. This PET technique might be useful for studying real-time liposomal trafficking and for tumor imaging.
众所周知，长循环脂质体可被动蓄积于荷瘤动物的肿瘤组织中。为评估此类脂质体在体内的行为，我们采用正电子发射断层扫描（PET）的非侵入性方法研究了脂质体的实时转运情况。在2-[¹⁸F]氟-2-脱氧葡萄糖（[2-¹⁸F]FDG）存在的情况下，制备了摩尔比为4:4:1的二棕榈酰磷脂酰胆碱、胆固醇和棕榈酰-D-葡萄糖醛酸（PGlcUA）组成的脂质体。将通过不同孔径滤膜挤出法制备的[2-¹⁸F]FDG标记的脂质体给予荷Meth A肉瘤的小鼠，并进行120分钟的PET扫描。用PGlcUA构建的小尺寸长循环脂质体（直径100 nm）倾向于在肿瘤组织中蓄积。相反，含有二棕榈酰磷脂酰甘油而非PGlcUA的对照脂质体（直径100 nm）在肝脏中蓄积。大尺寸含PGlcUA的脂质体（> 300 nm）也在肝脏以及脾脏中蓄积。时间-活性曲线表明，小的长循环脂质体（< 200 nm）在注射后立即短暂蓄积于肝脏，但肝脏中的蓄积量随时间呈下降趋势。这些数据表明，尽管大多数小的长循环脂质体保留在血流中，但一些脂质体一旦渗出到肝脏的间质空间中，会再次进入血流，最终在肿瘤组织中蓄积。这种PET技术可能有助于研究脂质体的实时转运以及肿瘤成像。
