High lung uptake of 99mTc-multilamellar liposomes after intravenous administration in rats and rabbits.

The study presents the results of our efforts to prepare liposomes with high lung uptake by modifying the liposome composition and size. Multilamellar liposomes composed of soya phosphatidylcholine and cholesterol (molar ratio 1:1), negatively charged with 0.1 mol sodium cholate were initially prepared. They were treated with SnF2 before (Lp) and after (Lp2) lyophilization and both types were labelled with 99mTc-NaTcO4 in saline solution. A fraction of small 99mTc-Lp2 was obtained by extrusion of negatively charged 99mTc liposomes through membrane filter (type 10 PCTE membranes) pore size 0.4 micron. The biodistribution of the 99mTc-Lp and 99mTc-Lp2 was compared after i.v. injection to rats [0.1 ml/2 mg lipid (3-4 MBq) per 100 g body weight]. After decapitation blood, liver and lung samples were collected and the relative concentrations of activity (RC) were obtained. 99mTc-Lp2 showed more prolonged blood circulation than 99mTc-Lp with a secondary moderate increase of the activity about 3 h and about 6 h postdose for 99mTc-Lp and 99mTc-Lp2, respectively. The lung localization of the 99mTc-Lp2 was clearly more intensive than the 99mTc-Lp localization (ratio of their maximal RC values 7:1). On the contrary, the 99mTc-Lp accumulated more intensively in the liver than the 99mTc-Lp2 (ratio of the RC values 5:1). The higher affinity of the smaller liposomes (99mTc-Lp2) to the lung was observed also in rabbits after i.v. administration of the extruded 99mTc-Lp2 fraction in the ear vein [0.1 ml/2 mg lipid (3-4 MBq) per 100 g body weight].(ABSTRACT TRUNCATED AT 250 WORDS)