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Ovarian cancer often leads to metastases which are initially confined to the intraperitoneal (i.p.) space. Immunoliposomes may be a promising tool for targeted delivery of radionuclides to these metastatic nodules. We treated SKOV3 ovarian carcinoma cells in vitro and in vivo with targeted liposomes to determine the liposomal uptake for potential future treatments using radionuclide-loaded liposomes. Liposomes containing mixtures of phosphatidylcholine (PtdCho):cholesterol (1:1 molar ratio) and polyethyleneglycol (PEG)-labeled lipids (6 mol% of total lipid) were formed using the extended hydration method (1). These liposomes were immunolabeled with the humanized monoclonal antibody trastuzumab (Herceptin), which is directed against her2/neu. In vitro, SKOV3 cells were incubated with these immunoliposomes for two hours, followed by trypsinization and extensive cell washing to remove unbound liposomes. Cells underwent dual phase extraction (2), followed by fully relaxed proton magnetic resonance spectroscopy to determine concentrations of cellular choline phospholipid metabolites. SKOV3 cells contained elevated levels of phosphocholine (PC) following incubation with liposomes composed of PtdCho. Both the ratio of PC to glycerophosphocholine (GPC) as well as cellular PC levels was 4-fold higher in cells that were treated with liposomes compared to untreated control cells. These findings indicate that liposomes were incorporated into SKOV3 ovarian cancer cells, and that PtdCho was most likely broken down to PC by phospholipases. In vivo, nude mice were injected i.p. with 5x106 SKOV3 cells which developed into tumor nodules on organs in the i.p. space. Two weeks post-injection, immunoliposomes were injected for imaging studies. Immunoliposomes were loaded with In-111 for μPET/CT imaging studies and fluorescence imaging was done utilizing a rhodamine-labeled lipid in the liposome structure. Imaging analysis demonstrated that liposomes were selectively targeted to the sites of tumor nodules. These findings indicate the potential of these systems for targeted delivery of radionuclides with little expected binding to normal cells. References: (1) Castile JD et al. Int J Pharm 188, 87 (1999) (2) Tyagi RK et al. Magn Reson Med 35, 194 (1996)

[Proc Amer Assoc Cancer Res, Volume 47, 2006]