Lopez-Berestein G, Kasi L, Rosenblum M G, Haynie T, Jahns M, Glenn H, Mehta R, Mavligit G M, Hersh E M
Cancer Res. 1984 Jan;44(1):375-8.
The pharmacokinetics, organ distribution, and 24-hr urinary excretion of negatively charged 99mTc-labeled multilamellar liposomes, composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 molar ratio, were studied in seven patients with cancer. The radiolabeled liposomes were administered i.v. in three doses: 150 mg/sq m of body surface area; 300 mg/sq m; and 450 mg/sq m of lipid. The dose of 99mTc was 4.8 to 7.6 mCi per patient. The plasma disappearance curve was biphasic (half-life alpha = 5.53 min, half-life beta = 289 min), suggesting a two-compartmental model of distribution. The calculated volume of distribution indicated considerable tissue retention of liposomes. This was confirmed by body imaging. Twenty-four hr after injection, liposomes were localized in organs rich in reticuloendothelial cells, i.e., liver [44.5 +/- 9.1% (S.E.)], spleen [25.5 +/- 7.7%], lung [14.5 +/- 4.9%], and bone marrow. Although the hepatic uptake accounted for more than 40% of the total uptake, the spleen retained liposomes at a higher density. Cumulative urinary excretion of radioactivity was 13.4 +/- 1.5% over 24 hr. Liposome administration was safe and devoid of any adverse side effects. The results provide a basis for the use of liposomes as potential target-specific and safe drug carriers in the treatment of pathological conditions that involve organs rich in reticuloendothelial cells.
在7名癌症患者中研究了由二肉豆蔻酰磷脂酰胆碱和二肉豆蔻酰磷脂酰甘油以7:3摩尔比组成的带负电荷的99mTc标记多层脂质体的药代动力学、器官分布和24小时尿排泄情况。放射性标记的脂质体通过静脉注射给予三个剂量：每平方米体表面积150毫克；300毫克/平方米；以及450毫克/平方米脂质。每位患者的99mTc剂量为4.8至7.6毫居里。血浆消失曲线呈双相（α半衰期 = 5.53分钟，β半衰期 = 289分钟），提示为二室分布模型。计算得到的分布容积表明脂质体在组织中有相当程度的滞留。这通过全身显像得到证实。注射后24小时，脂质体定位于富含网状内皮细胞的器官，即肝脏[44.5 +/- 9.1%（标准误）]、脾脏[25.5 +/- 7.7%]、肺[14.5 +/- 4.9%]和骨髓。尽管肝脏摄取占总摄取量的40%以上，但脾脏以更高的密度滞留脂质体。24小时内放射性的累积尿排泄量为13.4 +/- 1.5%。脂质体给药是安全的，且无任何不良副作用。这些结果为脂质体作为潜在的靶向特异性和安全药物载体用于治疗涉及富含网状内皮细胞器官的病理状况提供了依据。
