Doubly radiolabeled liposomes for pretargeted radioimmunotherapy

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• 作者：M. Mougin-Degraef ; C. Bourdeau ; E. Jestin ; C. Saï ; -Maurel ; M. Bourgeois ; P. Remaud-Le Saë ; c ; P. Thé ; drez ; J.-F. Gestin ; J. Barbet ; A. Faivre-Chauvet
• 关键词：Liposomes ; Radiolabeling ; Bolton– ; Hunter ; Pharmacokinetics ; Biodistribution
• 刊名：International Journal of Pharmaceutics
• 出版年：2007
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：1 November 2007
• 卷：344
• 期：1-2
• 页码：110-117
• 文件大小：646 K

摘要

The aim of this study was to design liposomes as radioactivity carriers for pretargeted radioimmunotherapy with favorable pharmacokinetic parameters. To monitor the liposomes integrity in vivo, their surface was radiolabeled with indium-111 bound to DTPA-derivatized phosphatidylethanolamine (DSPE-DTPA) and the aqueous phase was labeled by using an original active loading technique of radioiodinated Bolton–Hunter reagent (BH) that reacts with pre-encapsulated arginine to form a positively charged conjugate (¹²⁵I-BH-arginine). Different formulations of doubly radiolabeled liposomes were tested in vitro and in vivo to evaluate radiolabeling stability, integrity of the vesicles and their pharmacokinetics.

Radiolabeling yields were high (surface >75%, encapsulation >60%) and stable (>85%after 24 h in serum 37 °C). In vivo, the pharmacokinetic behavior of doubly radiolabeled liposomes was strongly dependant on the formulation. Blood clearance of PEGylated liposomes (DSPC/Chol/DSPE-DTPA/DSPE-PEG5%) was 0.15 mL/h compared to a conventional formulation (DSPC/Chol/DSPE-DTPA: clearance 1.44 mL/h). Non-encapsulated BH-arginine conjugate was quickly eliminated in urine (clearance 6.04 mL/h). Blood kinetics of the two radionuclides were similar and radiochromatographic profiles of mice serum confirmed the integrity of circulating liposomes. The significant reduction of activity uptake in organs after liposome catabolism (liver and spleen), achieved by the rapid renal elimination of ¹²⁵I-BH-arginine, should bring significant improvements for targeted radionuclide therapy with sterically-stabilized liposomes.