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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Clinical Pharmacology
Liposomes
Neoplasms
Half-Life
Spleen
Dimyristoylphosphatidylcholine
Drug Carriers
Body Surface Area
Liver
Radioactivity
Pharmacokinetics
Bone Marrow
Lipids
Lung
Injections

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

Clinical Pharmacology of 99mTc-labeled Liposomes in Patients with Cancer. / Rosenblum, Michael G.; Mavligit, Giora M.; Hersh, Evan M; Kasi, Leela; Haynie, Thomas; Glenn, Howard; Jahns, Monroe; Mehta, Reeta; Lopez-Berestein, Gabriel.

In: Cancer Research, Vol. 44, No. 1, 01.01.1984, p. 375-378.

Research output: Contribution to journalArticle

Rosenblum, MG, Mavligit, GM, Hersh, EM, 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, vol. 44, no. 1, pp. 375-378.
Rosenblum MG, Mavligit GM, Hersh EM, Kasi L, Haynie T, Glenn H et al. Clinical Pharmacology of 99mTc-labeled Liposomes in Patients with Cancer. Cancer Research. 1984 Jan 1;44(1):375-378.
Rosenblum, Michael G. ; Mavligit, Giora M. ; Hersh, Evan M ; Kasi, Leela ; Haynie, Thomas ; Glenn, Howard ; Jahns, Monroe ; Mehta, Reeta ; Lopez-Berestein, Gabriel. / Clinical Pharmacology of 99mTc-labeled Liposomes in Patients with Cancer. In: Cancer Research. 1984 ; Vol. 44, No. 1. pp. 375-378.
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