Use of radiolabeled hexadecyl cholesteryl ether as a liposome marker

Pool, Gary L.; French, M. E.; Edwards, Ross A.; Huang, Leaf; Lumb, Roger H.

doi:10.1007/bf02535225

Cited by 83 publications

(34 citation statements)

References 26 publications

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“…As required, [ 14 C]-CHE was added to the dissolved lipids as a nonexchangeable, nonmetabolizable marker. 29 Antisense was dissolved in 300 mM citrate buffer, pH 4.0 at a concentration of 3.33 mg/ml, with the addition of sufficient [ 3 H]-H2A-ASO or [ 3 H]-VEGF-ASO for quantitation. Typical specific activities were 900 dpm/µg for antisense and 130 dpm/µg for lipid.…”

Section: Methodsmentioning

confidence: 99%

Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model

Waterhouse¹,

Dragowska²,

Gelmon³

et al. 2004

Cancer Biology & Therapy

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The nature of anti-cancer therapeutics is currently undergoing a paradigm change, with biologic agents slowly being introduced into the therapeutic armory, displacing or complimenting the traditionally used cytotoxic agents. These new agents include monoclonal antibodies, recombinant DNA, antisense oligonucleotides (ASO) and others. To assess the new therapeutics, new predictive models are required. Utilizing the MDA435/LCC6 human breast cancer xenograft model, the pharmacokinetic behavior of antisense oligonucleotides targeted against vascular endothelial growth factor and HER-2/neu was assessed. For pharmacodynamic analysis, ASO in buffer or encapsulated in a liposomal formulation were injected intravenously or intraperitoneally into MDA435/LCC6 ascites tumor-bearing mice. Plasma antisense elimination, tissue distribution, total peritoneal antisense and peritoneal cell associated antisense levels were determined. Liposomal encapsulation led to significant decreases in the plasma elimination rate, as evidenced by an approximate 10-fold increase in mean AUC over 24 hours, as well as enhanced peritoneal cell delivery in mice bearing ascites tumors. Tissue distribution studies of both free and liposome encapsulated ASO indicated that ASO distribution was dictated primarily by the liposomal carrier when administered in liposomal form.

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Section: Methodsmentioning

confidence: 99%

Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model

Waterhouse¹,

Dragowska²,

Gelmon³

et al. 2004

Cancer Biology & Therapy

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“…Liposome size was verified by dynamic light scattering using a Malvern Zetasizer 5000 (Malvern Instruments Ltd.). [ 3 H]CHE was added as a nonmetabolized, nonexchangeable lipid tracer (31,33).…”

Section: Preparation Of Doxorubicin-loaded Liposomesmentioning

confidence: 99%

Antitumor activity of an epithelial cell adhesion molecule–targeted nanovesicular drug delivery system

Hussain

Plückthun

Allen

et al. 2007

Molecular Cancer Therapeutics

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Site-specific delivery of anticancer agents to tumors represents a promising therapeutic strategy because it increases efficacy and reduces toxicity to normal tissues compared with untargeted drugs. Sterically stabilized immunoliposomes (SIL), guided by antibodies that specifically bind to well internalizing antigens on the tumor cell surface, are effective nanoscale delivery systems capable of accumulating large quantities of anticancer agents at the tumor site. The epithelial cell adhesion molecule (EpCAM) holds major promise as a target for antibodybased cancer therapy due to its abundant expression in many solid tumors and its limited distribution in normal tissues. We generated EpCAM-directed immunoliposomes by covalently coupling the humanized single-chain Fv antibody fragment 4D5MOCB to the surface of sterically stabilized liposomes loaded with the anticancer agent doxorubicin. In vitro, the doxorubicin-loaded immunoliposomes (SIL-Dox) showed efficient cell binding and internalization and were significantly more cytotoxic against EpCAM-positive tumor cells than nontargeted liposomes (SL-Dox). In athymic mice bearing established human tumor xenografts, pharmacokinetic and biodistribution analysis of SIL-Dox revealed long circulation times in the blood with a half-life of 11 h and effective time-dependent tumor localization, resulting in up to 15% injected dose per gram tissue. These favorable pharmacokinetic properties translated into potent antitumor activity, which resulted in significant growth inhibition (compared with control mice), and was more pronounced than that of doxorubicin alone and nontargeted SL-Dox at low, nontoxic doses. Our data show the promise of EpCAM-directed nanovesicular drug delivery for targeted therapy of solid tumors.

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“…Radioactivity was assayed with Plasmasol as scintillation mixture. Blood volume was taken as 77.8 ml kg-' body weight (Wish et al, 1950 (Stein et al, 1980;Pool et al, 1982). Figure 1 shows that immunoliposomes bound to the tumour cells to a higher extent (9.5-13-fold) than non-targeted liposomes, which showed hardly any binding.…”

Section: Binding Of Dxr-immunoliposomes To Ovarian Cancer Cells In Vitromentioning

confidence: 99%

Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo

Vingerhoeds

Steerenberg²,

Hendriks³

et al. 1996

Br J Cancer

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Use of radiolabeled hexadecyl cholesteryl ether as a liposome marker

Cited by 83 publications

References 26 publications

Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model

Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model

Antitumor activity of an epithelial cell adhesion molecule–targeted nanovesicular drug delivery system

Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo

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