Essien H, Lai J Y, Hwang K J
School of Pharmacy, University of Southern California, Los Angeles 90033.
J Med Chem. 1988 May;31(5):898-901. doi: 10.1021/jm00400a002.
The synthesis, binding of radioactive cations, liposomal encapsulation, and biodistribution of the oxidized-inulin reaction product with ethylenediamine and diethylenetriaminepentaacetic acid (4) are described. The four-step synthesis of the inulin derivative proceeded in a good overall yield of 72%. The complex of the inulin derivative with either 67Ga3+ or 111In3+ was stable in vivo and did not readily distribute into tissues, being excreted primarily in urine after intravenous administration to mice. The liposome-entrapped inulin derivative can be loaded with radioactive heavy metal cations by mobile ionophores in high radiochemical yields of 80-91%. Following the intravenous administration of the liposomal encapsulation of the indium-111-labeled inulin derivative, the entrapped compound had a biodistribution characteristic of liposomes and allowed an estimation of the extent of the intracellular uptake of liposomes. The ability of the inulin derivative to chelate many different types of metals will allow the use of this probe for studying subtle differences in tissue distribution resulting from different drug targeting or delivery protocols in the same animal by multiple labeling techniques. Moreover, the chelate-conjugated inulin permits studies of the applications of drug delivery systems in primates or human subjects by noninvasive techniques such as gamma-scintigraphic or nuclear magnetic resonance imaging methods.
本文描述了氧化菊粉与乙二胺和二乙烯三胺五乙酸（4）反应产物的合成、放射性阳离子的结合、脂质体包封及生物分布。菊粉衍生物的四步合成总产率良好，为72%。菊粉衍生物与67Ga3+或111In3+形成的配合物在体内稳定，不易分布到组织中，静脉注射给小鼠后主要经尿液排泄。脂质体包裹的菊粉衍生物可通过流动离子载体以80 - 91%的高放射化学产率负载放射性重金属阳离子。静脉注射111铟标记的菊粉衍生物脂质体包封物后，包裹的化合物具有脂质体的生物分布特征，并可估计脂质体的细胞内摄取程度。菊粉衍生物螯合多种不同类型金属的能力将使该探针可用于通过多重标记技术研究同一动物中不同药物靶向或递送方案导致的组织分布细微差异。此外，螯合共轭菊粉允许通过γ闪烁显像或核磁共振成像等非侵入性技术研究药物递送系统在灵长类动物或人类受试者中的应用。
