Abstract
The possible use of liposomes (phospholipid vesicles) to direct cytotoxic drugs to tumours has led us to investigate the tissue localization of i.v. injected 99m-Tc-labelled liposomes in cancer patients. Twenty mg or 300 mg doses of liposomal lipid (7:2:1 molar ratio of phosphatidylcholine : cholesterol : phosphatidic acid) were used in a study of 13 patients with advanced cancer and one with polycythaemia rubra vera (PRV). In all cases except the patient with PRV the major site of uptake of the label was the liver and spleen. In the patient with PRV the liver uptake was greatly reduced and the major site of uptake was found in regions corresponding to marrow. With the exception of one patient with a primary hepatoma, there was no significant tumour uptake of the label.
Full text
PDF








Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams D. H., Joyce G., Richardson V. J., Ryman B. E., Wiśniewski H. M. Liposome toxicity in the mouse central nervous system. J Neurol Sci. 1977 Mar;31(2):173–179. doi: 10.1016/0022-510x(77)90104-6. [DOI] [PubMed] [Google Scholar]
- Anghileri L. J., Firusian N., Brucksch K. P. In vivo distribution of 99mTc-labeled liposomes. J Nucl Biol Med. 1976 Oct-Dec;20(4):165–167. [PubMed] [Google Scholar]
- BUSCH H., FUJIWARA E., FIRSZT D. C. Studies on the metabolism of radioactive albumin in tumor-bearing rats. Cancer Res. 1961 Apr;21:371–377. [PubMed] [Google Scholar]
- Bangham A. D., Standish M. M., Watkins J. C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965 Aug;13(1):238–252. doi: 10.1016/s0022-2836(65)80093-6. [DOI] [PubMed] [Google Scholar]
- Belchetz P. E., Crawley J. C., Braidman I. P., Gregoriadis G. Treatment of Gaucher's disease with liposome-entrapped glucocerebroside: beta-glucosidase. Lancet. 1977 Jul 16;2(8029):116–117. doi: 10.1016/s0140-6736(77)90123-4. [DOI] [PubMed] [Google Scholar]
- Black C. D., Gregoriadis G. Interaction of liposomes with blood plasma proteins. Biochem Soc Trans. 1976;4(2):253–256. doi: 10.1042/bst0040253a. [DOI] [PubMed] [Google Scholar]
- Bruni A., Toffano G., Leon A., Boarato E. Pharmacological effects of phosphatidylserine liposomes. Nature. 1976 Mar 25;260(5549):331–333. doi: 10.1038/260331a0. [DOI] [PubMed] [Google Scholar]
- Colley C. M., Ryman B. E. Liposomes as carriers in vivo for methotrexate. Biochem Soc Trans. 1975;3(1):157–159. doi: 10.1042/bst0030157. [DOI] [PubMed] [Google Scholar]
- Dapergolas G., Neerunjun E. D., Gregoriadis G. Penetration of target areas in the rat by liposome-associated bleomycin, glucose oxidase and insulin. FEBS Lett. 1976 Apr 1;63(2):235–239. doi: 10.1016/0014-5793(76)80102-0. [DOI] [PubMed] [Google Scholar]
- EASTY G. C., YARNELL M. M., ANDREWS R. D. THE UPTAKE OF PROTEINS BY NORMAL AND TUMOUR CELLS IN VITRO. Br J Cancer. 1964 Jun;18:354–367. doi: 10.1038/bjc.1964.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GHOSE T., NAIRN R. C., FOTHERGILL J. E. Uptake of proteins by malignant cells. Nature. 1962 Dec 15;196:1108–1109. doi: 10.1038/1961108b0. [DOI] [PubMed] [Google Scholar]
- Gregoriadis G. The carrier potential of liposomes in biology and medicine (first of two parts). N Engl J Med. 1976 Sep 23;295(13):704–710. doi: 10.1056/NEJM197609232951305. [DOI] [PubMed] [Google Scholar]
- Gregoriadis G., Wills E. J., Swain C. P., Tavill A. S. Drug-carrier potential of liposomes in cancer chemotherapy. Lancet. 1974 Jun 29;1(7870):1313–1316. doi: 10.1016/s0140-6736(74)90682-5. [DOI] [PubMed] [Google Scholar]
- Juliano R. L., Stamp D. Pharmacokinetics of liposome-encapsulated anti-tumor drugs. Studies with vinblastine, actinomycin D, cytosine arabinoside, and daunomycin. Biochem Pharmacol. 1978 Jan 1;27(1):21–27. doi: 10.1016/0006-2952(78)90252-6. [DOI] [PubMed] [Google Scholar]
- Kobayashi T., Kataoka T., Tsukagoshi S., Sakurai Y. Enhancement of anti-tumor activity of 1-beta-D-arabinofuranosylcytosine by encapsulation in liposomes. Int J Cancer. 1977 Oct 15;20(4):581–587. doi: 10.1002/ijc.2910200416. [DOI] [PubMed] [Google Scholar]
- Kobayashi T., Kataoka T., Tsukagoshi S., Sakurai Y. Enhancement of anti-tumor activity of 1-beta-D-arabinofuranosylcytosine by encapsulation in liposomes. Int J Cancer. 1977 Oct 15;20(4):581–587. doi: 10.1002/ijc.2910200416. [DOI] [PubMed] [Google Scholar]
- Kosloski M. J., Rosen F., Milholland R. J., Papahadjopoulos D. Effect of lipid vesicle (liposome) encapsulation of methotrexate on its chemotherapeutic efficacy in solid rodent tumors. Cancer Res. 1978 Sep;38(9):2848–2853. [PubMed] [Google Scholar]
- Lokich J. J., Drum D. E., Kaplan W. Hepatic toxicity of nitrosourea analogues. Clin Pharmacol Ther. 1974 Aug;16(2):363–367. doi: 10.1002/cpt1974162363. [DOI] [PubMed] [Google Scholar]
- Mego J. L., McQueen J. D. The uptake of labeled proteins by particulate fractions of tumor and normal tissues after injection into mice. Cancer Res. 1965 Jul;25(6):865–869. [PubMed] [Google Scholar]
- Neerunjun E. D., Hunt R., Gregoriadis G. Fate of a liposome-associated agent injected into normal and tumour-bearing rodents: attempts to improve localization in tumour tissues [proceedings]. Biochem Soc Trans. 1977;5(5):1380–1383. doi: 10.1042/bst0051380. [DOI] [PubMed] [Google Scholar]
- Richardson V. J., Jeyasingh K., Jewkes R. F., Ryman B. E., Tattersall M. H. Possible tumor localization of Tc-99m-labeled liposomes: effects of lipid composition, charge, and liposome size. J Nucl Med. 1978 Sep;19(9):1049–1054. [PubMed] [Google Scholar]
- Richardson V. J., Jeyasingh K., Jewkes R. F., Ryman B. E., Tattersall M. H. Properties of [99mTc] technetium-labelled liposomes in normal and tumour-bearing rats. Biochem Soc Trans. 1977;5(1):290–291. doi: 10.1042/bst0050290. [DOI] [PubMed] [Google Scholar]
- Richardson V. J., Ryman B. E., Jewkes R. F., Tattersall M. H., Newlands E. S. 99mTc-labelled liposomes preparation of radiopharmaceutical and its distribution in a hepatoma patient. Int J Nucl Med Biol. 1978;5(2-3):118, 121-2, 123. doi: 10.1016/0047-0740(78)90041-4. [DOI] [PubMed] [Google Scholar]
- Segal A. W., Gregoriadis G., Lavender J. P., Tarin D., Peters T. J. Tissue and hepatic subcellular distribution of liposomes containing bleomycin after intravenous administration to patients with neoplasms. Clin Sci Mol Med. 1976 Oct;51(4):421–425. doi: 10.1042/cs0510421. [DOI] [PubMed] [Google Scholar]
- Sharbaugh R. J., Grogan J. B. Suppression of reticuloendothelial function in the rat with cyclophosphamide. J Bacteriol. 1969 Oct;100(1):117–122. doi: 10.1128/jb.100.1.117-122.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steger L. D., Desnick R. J. Enzyme therapy. VI: Comparative in vivo fates and effects on lysosomal integrity of enzyme entrapped in negatively and positively charged liposomes. Biochim Biophys Acta. 1977 Feb 4;464(3):530–546. doi: 10.1016/0005-2736(77)90028-1. [DOI] [PubMed] [Google Scholar]
- Trouet A., Deprez-de Campeneere D., De Duve C. Chemotherapy through lysosomes with a DNA-daunorubicin complex. Nat New Biol. 1972 Sep 27;239(91):110–112. doi: 10.1038/newbio239110a0. [DOI] [PubMed] [Google Scholar]
- Tyrrell D. A., Richardson V. J., Ryman B. E. The effect of serum protein fractions on liposome-cell interactions in cultured cells and the perfused rat liver. Biochim Biophys Acta. 1977 Apr 27;497(2):469–480. doi: 10.1016/0304-4165(77)90204-5. [DOI] [PubMed] [Google Scholar]
- Tyrrell D. A., Ryman B. E., Keeton B. R., Dubowitz V. Use of liposomes in treating type II glycogenosis. Br Med J. 1976 Jul 10;2(6027):88–88. doi: 10.1136/bmj.2.6027.88. [DOI] [PMC free article] [PubMed] [Google Scholar]


