CLINICAL-PHARMACOLOGY OF TC-99M-LABELED LIPOSOMES IN PATIENTS WITH CANCER

Abstract

The pharmacokinetics, organ distribution and 24-h urinary excretion of negatively charged 99mTc-labeled multilamellar liposomes, composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 molar ratio, were studied in 7 patients with cancer. The radiolabeled liposomes were administered i.v. in 3 doses: 150 mg/m2 of body surface area; 300 mg/m2; and 450 mg/m2 of lipid. The dose of 99mTc was 4.8-7.6 mCi/patient. The plasma disappearance curve was biphasic (half-life .alpha. = 5.53 min, half-life .beta. = 289 min), suggesting a 2-compartmental model of distribution. The calculated volume of distribution indicated considerable tissue retention of liposomes. This was confirmed by body imaging. After injection at 24 h, liposomes were localized in organs rich in reticuloendothelial cells, i.e., liver [44.5 .+-. 9.1% (SE)], spleen [25.5 .+-. 7.7%], lung [14.5 .+-. 4.9%] and bone marrow. Although the hepatic uptake accounted for > 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 h. 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.