Abstract
The relationship between tumour size and uptake of111In-DTPA-labelled pegylated liposomes has been examined in a human head and neck cancer xenograft model in nude mice. The mean tumour uptake of111In-labelled pegylated liposomes at 24 hours was 7.2 ± 6.6% ID/g. Liposome uptake for tumours < 0.1 g, 0.1–1.0 g and > 1.0 g was 15.1 ± 10.8, 5.9 ± 2.2 and 3.0 ± 1.3% ID/g, respectively. An inverse correlation between tumour weight and liposome uptake was observed by both Spearman’s rank correlation test (r s= – 0.573, P< 0.001) and Pearson’s correlation coefficient (r s= – 0.555, P< 0.001). For 18 tumours with macroscopic central necrosis, the ratio of uptake in the tumour rim relative to the necrotic tumour core was 11.2 ± 6.4. Measurement of tumour vascular volume for tumours of various sizes revealed an inverse correlation between tumour weight and tumour vascular volume (Spearman’s rank correlation test, r s= – 0.598, P< 0.001), consistent with poor or heterogeneous vascularization of larger tumours. These data have important implications for the clinical application of pegylated liposome targeted strategies for solid cancers which are discussed in detail. © 2000 Cancer Research Campaign
Keywords: pegylated liposome, tumour targeting, vascularity, xenograft
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Footnotes
STEALTH® liposomes are a registered trademark of SEQUUS Pharmaceuticals Inc. (Menlo Park, CA, USA)
Selected References
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- 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]
- Beaney R. P., Lammertsma A. A., Jones T., McKenzie C. G., Halnan K. E. Positron emission tomography for in-vivo measurement of regional blood flow, oxygen utilisation, and blood volume in patients with breast carcinoma. Lancet. 1984 Jan 21;1(8369):131–134. doi: 10.1016/s0140-6736(84)90063-1. [DOI] [PubMed] [Google Scholar]
- Bogner J. R., Kronawitter U., Rolinski B., Truebenbach K., Goebel F. D. Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma. J Acquir Immune Defic Syndr. 1994 May;7(5):463–468. [PubMed] [Google Scholar]
- EAGLE H. Propagation in a fluid medium of a human epidermoid carcinoma, strain KB. Proc Soc Exp Biol Med. 1955 Jul;89(3):362–364. doi: 10.3181/00379727-89-21811. [DOI] [PubMed] [Google Scholar]
- Gabizon A. A. Liposomal anthracyclines. Hematol Oncol Clin North Am. 1994 Apr;8(2):431–450. [PubMed] [Google Scholar]
- Gabizon A., Catane R., Uziely B., Kaufman B., Safra T., Cohen R., Martin F., Huang A., Barenholz Y. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res. 1994 Feb 15;54(4):987–992. [PubMed] [Google Scholar]
- Gabizon A., Papahadjopoulos D. Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6949–6953. doi: 10.1073/pnas.85.18.6949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gabizon A., Price D. C., Huberty J., Bresalier R. S., Papahadjopoulos D. Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies. Cancer Res. 1990 Oct 1;50(19):6371–6378. [PubMed] [Google Scholar]
- Goebel F. D., Goldstein D., Goos M., Jablonowski H., Stewart J. S. Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi's sarcoma. The International SL-DOX Study Group. Br J Cancer. 1996 Apr;73(8):989–994. doi: 10.1038/bjc.1996.193. [DOI] [PMC free article] [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]
- Harrison M., Tomlinson D., Stewart S. Liposomal-entrapped doxorubicin: an active agent in AIDS-related Kaposi's sarcoma. J Clin Oncol. 1995 Apr;13(4):914–920. doi: 10.1200/JCO.1995.13.4.914. [DOI] [PubMed] [Google Scholar]
- Huang S. K., Lee K. D., Hong K., Friend D. S., Papahadjopoulos D. Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice. Cancer Res. 1992 Oct 1;52(19):5135–5143. [PubMed] [Google Scholar]
- Jain R. K., Baxter L. T. Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. Cancer Res. 1988 Dec 15;48(24 Pt 1):7022–7032. [PubMed] [Google Scholar]
- Jain R. K. Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors. Cancer Res. 1990 Feb 1;50(3 Suppl):814s–819s. [PubMed] [Google Scholar]
- Kalofonos H., Rowlinson G., Epenetos A. A. Enhancement of monoclonal antibody uptake in human colon tumor xenografts following irradiation. Cancer Res. 1990 Jan 1;50(1):159–163. [PubMed] [Google Scholar]
- Klibanov A. L., Maruyama K., Torchilin V. P., Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990 Jul 30;268(1):235–237. doi: 10.1016/0014-5793(90)81016-h. [DOI] [PubMed] [Google Scholar]
- Lasic D. D., Papahadjopoulos D. Liposomes revisited. Science. 1995 Mar 3;267(5202):1275–1276. doi: 10.1126/science.7871422. [DOI] [PubMed] [Google Scholar]
- Rowlinson-Busza G., Maraveyas A., Epenetos A. A. Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. Br J Cancer. 1995 Apr;71(4):660–665. doi: 10.1038/bjc.1995.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sands H., Shah S. A., Gallagher B. M. Vascular volume and permeability of human and murine tumors grown in athymic mice. Cancer Lett. 1985 May;27(1):15–21. doi: 10.1016/0304-3835(85)90004-7. [DOI] [PubMed] [Google Scholar]
- Song C. W., Levitt S. H. Effect of x irradiation on vascularity of normal tissues and experimental tumor. Radiology. 1970 Feb;94(2):445–447. doi: 10.1148/94.2.445. [DOI] [PubMed] [Google Scholar]