Distribution and pharmacology of intravenous 99mTc-labeled multilamellar liposomes in rats and mice

• Published in: International journal of nuclear medicine & biology Vol. 11; no. 1; pp. 35 - 37
• Main Authors: Kasi, Leela P., Lopez-Berestein, Gabriel, Mehta, Kapil, Rosenblum, Michael, Glenn, Howard J., Haynie, Thomas P., Mavligit, Giora, Hersh, Evan M.
• Format: Journal Article
• Language: English
• Published: Tarrytown, NY Elsevier Inc 1984; Elsevier
• Subjects: Animals; Biological and medical sciences; Contrast media. Radiopharmaceuticals; Injections, Intravenous; Kinetics; Liposomes - administration & dosage; Male; Medical sciences; Mice; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Technetium; Tissue Distribution; Vertebrata; Mammalia; Rat; Mouse; Reticuloendothelial system; Animal; Rodentia; Dosage form; Liposome; Radioisotope; Metabolism; Pharmacokinetics
• ISSN: 0047-0740
• DOI: 10.1016/0047-0740(84)90028-7

The use of liposomes for the delivery of macrophage activators offers a new approach for the selective targeting of antitumor therapy. We have investigated the distribution, retention, and pharmacology of multilamellar liposomes (phosphatidylserine (PS): phosphatidylcholine (PC) 3:7) on i.v. injection in normal rats. Sprague-Dawley rats were injected with doses varying from 300 to 1000 mg/kg of 99mTc-liposomes. The organ distribution of doses ranging from 300 to 500 mg/kg showed 45% mean uptake by liver, 25% by spleen, and 4% by lung. At higher doses of 800–1000 mg/kg, uptake in the lung increased significantly to 9 ± 3%. Whole body retention at 24 h after i.v. injection in Hale Stoner mice was 70%. The blood disappearance curve was biphasic and compared with the free isotope, a decrease was observed in the initial a phase t 1 2 while the terminal phase t 1 2 increased by 100%. These data suggest that encapsulation prolongs the initial distribution to the peripheral compartments and that higher doses may increase uptake by organs other than the liver.