Clinical Pharmacology of 99mTc-labeled Liposomes in Patients with Cancer

Michael G. Rosenblum, Giora M. Mavligit, Evan M. Hersh, Leela Kasi, Thomas Haynie, Howard Glenn, Monroe Jahns, Reeta Mehta, Gabriel Lopez-Berestein

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104 Scopus citations

Abstract

The pharmacokinetics, organ distribution, and 24-hr urinary excretion of negatively charged 99Tc-labeled multilamellar liposomes, composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 molar ratio, were studied in seven patients with cancer. The radiolabeled liposomes were administered i.v. in three doses: 150 mg/sq m of body surface area; 300 mg/sq m; and 450 mg/sq m of lipid. The dose of Tc was 4.8 to 7.6 mCi per patient. The plasma disappearance curve was Diphasic (half-life α= 5.53 min, half-life β= 289 min), suggesting a two-compartmental model of distribution. The calculated volume of distribution indicated considerable tissue retention of liposomes. This was confirmed by body imaging. Twenty-four hr after injection, liposomes were localized in organs rich in reticuloendothelial cells, i.e., liver [44.5 ± 9.1% (S.E.)], spleen [25.5 ± 7.7%], lung [14.5 ± 4.9%], and bone marrow. Although the hepatic uptake accounted for more than 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 hr. 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.

Original languageEnglish (US)
Pages (from-to)375-378
Number of pages4
JournalCancer Research
Volume44
Issue number1
StatePublished - Jan 1 1984

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Rosenblum, M. G., Mavligit, G. M., Hersh, E. M., Kasi, L., Haynie, T., Glenn, H., Jahns, M., Mehta, R., & Lopez-Berestein, G. (1984). Clinical Pharmacology of 99mTc-labeled Liposomes in Patients with Cancer. Cancer Research, 44(1), 375-378.