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| Publications [#168987] of Mark W. Dewhirst
Papers Published
- S Shan, C Flowers, CD Peltz, H Sweet, N Maurer, EJ Kwon, A Krol, F Yuan, MW Dewhirst, Preferential extravasation and accumulation of liposomal vincristine in tumor comparing to normal tissue enhances antitumor activity.,
Cancer chemotherapy and pharmacology, Germany, vol. 58 no. 2
(August, 2006),
pp. 245-55, ISSN 0344-5704
(last updated on 2009/12/31)
Abstract:
To quantitatively evaluate the extravasation, accumulation and selectivity to tumor tissues of liposomal vincristine (LV), dorsal skin-fold window chambers on athymic mice with or without LX-1, a human small cell lung cancer, xenograft implants and fluorescent intravital microscopy imaging were used. In vitro studies show that minimal loss of fluorescence marker DiI from liposomes occurs after 4 days of inoculation in murine plasma, and the release profiles of DiI-LV and LV were essentially the same with approximately 40% of the encapsulated vincristine sulfate (VCR) released after 26 h. Significantly faster extravasation of DiI-LV from tumor vessels was shown compared to non-tumor tissue after single dose i.v. administration. The relative interstitial amounts at 60 min (RIA(60)) for tumor and non-tumor tissues were 0.837+/-0.314 and 0.012+/-0.091, respectively (P=0.01). DiI-LV accumulation was significantly higher in tumor than in normal tissue, which continued beyond 48 h. Both DiI-LV and LV showed significant antitumor effects in window chambers and in flank tumors, compared with controls and VLS alone. The preferential extravasation of DiI-LV from tumor vasculature as well as its differential retention in tumor tissue provides the basis for the enhancement in antitumor activity of LV over VCR.
Keywords:
Animals • Antineoplastic Agents, Phytogenic • Cell Line, Tumor • Extravasation of Diagnostic and Therapeutic Materials* • Fluorescent Dyes • Humans • Liposomes • Mice • Mice, Nude • Microscopy, Fluorescence • Neoplasm Transplantation • Neovascularization, Pathologic • Tissue Distribution • Vincristine • blood • drug therapy • pharmacokinetics* • pharmacology*
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