Erschienen in:
01.08.2006 | Original Article
Preferential extravasation and accumulation of liposomal vincristine in tumor comparing to normal tissue enhances antitumor activity
verfasst von:
Siqing Shan, Clay Flowers, Cathy D. Peltz, Heather Sweet, Norbert Maurer, Eun-Joo Gina Kwon, Ave Krol, Fan Yuan, Mark W. Dewhirst
Erschienen in:
Cancer Chemotherapy and Pharmacology
|
Ausgabe 2/2006
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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 (RIA60) 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.