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Alkylphosphocholine
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Hansjörg Eibl – One of the best experts on this subject based on the ideXlab platform.
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Erufosine suppresses breast cancer in vitro and in vivo for its activity on PI3K, c-Raf and Akt proteins
Journal of cancer research and clinical oncology, 2012Co-Authors: Ilina K. Dineva, Hansjörg Eibl, Maya M. Zaharieva, Spiro Konstantinov, Martin R. BergerAbstract:Purpose This study investigated the antineoplastic effect of the membrane active Alkylphosphocholine erufosine in breast carcinoma models in vitro and in vivo and determined its influence on the PI3K/Akt and Ras/Raf/MAPK signaling pathways.
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Pharmacokinetics and biodistribution of Erufosine in nude mice – implications for combination with radiotherapy
Radiation oncology (London England), 2009Co-Authors: Guido Henke, Hansjörg Eibl, Lars H. Lindner, Michael Vogeser, Jürgen Wörner, Arndt Christian Müller, Michael Bamberg, Kirsten Wachholz, Claus Belka, Verena JendrossekAbstract:Background Alkylphosphocholines represent promising antineoplastic drugs that induce cell death in tumor cells by primary interaction with the cell membrane. Recently we could show that a combination of radiotherapy with Erufosine, a paradigmatic intravenously applicable Alkylphosphocholine, in vitro leads to a clear increase of irradiation-induced cell death. In view of a possible combination of Erufosine and radiotherapy in vivo we determined the pharmacokinetics and bioavailability as well as the tolerability of Erufosine in nude mice.
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Pharmacokinetics and biodistribution of Erufosine in nude mice – implications for combination with radiotherapy
Radiation Oncology, 2009Co-Authors: Guido Henke, Hansjörg Eibl, Lars H. Lindner, Michael Vogeser, Jürgen Wörner, Arndt Christian Müller, Michael Bamberg, Kirsten Wachholz, Claus Belka, Verena JendrossekAbstract:Background Alkylphosphocholines represent promising antineoplastic drugs that induce cell death in tumor cells by primary interaction with the cell membrane. Recently we could show that a combination of radiotherapy with Erufosine, a paradigmatic intravenously applicable Alkylphosphocholine, in vitro leads to a clear increase of irradiation-induced cell death. In view of a possible combination of Erufosine and radiotherapy in vivo we determined the pharmacokinetics and bioavailability as well as the tolerability of Erufosine in nude mice. Methods NMRI (nu/nu) nude mice were treated by intraperitoneal or subcutaneous injections of 5 to 40 mg/kg body weight Erufosine every 48 h for one to three weeks. Erufosine-concentrations were measured in brain, lungs, liver, small intestine, colon, spleen, kidney, stomach, adipoid tissue, and muscle by tandem-mass spectroscopy. Weight course, blood cell count and clinical chemistry were analyzed to evaluate general toxicity. Results Intraperitoneal injections were generally well tolerated in all dose groups but led to a transient loss of the bodyweight (
John S. Kuo – One of the best experts on this subject based on the ideXlab platform.
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Diapeutic cancer-targeting Alkylphosphocholine analogs may advance management of brain malignancies.
CNS oncology, 2016Co-Authors: Ray R. Zhang, Kyle I. Swanson, Lance T. Hall, Jamey P. Weichert, John S. KuoAbstract:The following is a special report on Alkylphosphocholine analogs as targeted imaging and therapy agents for cancer, and their potential role in diagnosis and treatment in glioblastoma and brain metastases. These novel cancer-targeting agents display impressive tumor avidity with low background in the normal brain, and multimodal diagnostic imaging and therapy capabilities. The use of these agents may significantly improve diagnosis, treatment and post-treatment follow-up in patients with brain malignancies
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Analysis of Cancer-Targeting Alkylphosphocholine Analogue Permeability Characteristics Using a Human Induced Pluripotent Stem Cell Blood–Brain Barrier Model
Molecular pharmaceutics, 2016Co-Authors: Paul A. Clark, Ray R. Zhang, John S. Kuo, Jamey P. Weichert, Abraham Al-ahmad, Tongcheng Qian, Hannah K. Wilson, Sean P. Palecek, Eric V. ShustaAbstract:Cancer-targeting Alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure–activity studies. While they strongly label human brain cancers associated with disrupted blood–brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). This in vitro BBB system has reproducibly consistent high barrier integrity marked by high transendothelial electrical resistance (TEER > 1500 Ω-cm2) and functional expression of drug efflux transporters. The radioiodinated an…
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analysis of cancer targeting Alkylphosphocholine analogue permeability characteristics using a human induced pluripotent stem cell blood brain barrier model
Molecular Pharmaceutics, 2016Co-Authors: Paul A. Clark, Ray R. Zhang, John S. Kuo, Jamey P. Weichert, Tongcheng Qian, Hannah K. Wilson, Sean P. Palecek, Abraham Alahmad, Eric V. ShustaAbstract:Cancer-targeting Alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure–activity studies. While they strongly label human brain cancers associated with disrupted blood–brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). This in vitro BBB system has reproducibly consistent high barrier integrity marked by high transendothelial electrical resistance (TEER > 1500 Ω-cm2) and functional expression of drug efflux transporters. The radioiodinated an…
Jamey P. Weichert – One of the best experts on this subject based on the ideXlab platform.
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Diapeutic cancer-targeting Alkylphosphocholine analogs may advance management of brain malignancies.
CNS oncology, 2016Co-Authors: Ray R. Zhang, Kyle I. Swanson, Lance T. Hall, Jamey P. Weichert, John S. KuoAbstract:The following is a special report on Alkylphosphocholine analogs as targeted imaging and therapy agents for cancer, and their potential role in diagnosis and treatment in glioblastoma and brain metastases. These novel cancer-targeting agents display impressive tumor avidity with low background in the normal brain, and multimodal diagnostic imaging and therapy capabilities. The use of these agents may significantly improve diagnosis, treatment and post-treatment follow-up in patients with brain malignancies
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Analysis of Cancer-Targeting Alkylphosphocholine Analogue Permeability Characteristics Using a Human Induced Pluripotent Stem Cell Blood–Brain Barrier Model
Molecular pharmaceutics, 2016Co-Authors: Paul A. Clark, Ray R. Zhang, John S. Kuo, Jamey P. Weichert, Abraham Al-ahmad, Tongcheng Qian, Hannah K. Wilson, Sean P. Palecek, Eric V. ShustaAbstract:Cancer-targeting Alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure–activity studies. While they strongly label human brain cancers associated with disrupted blood–brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). This in vitro BBB system has reproducibly consistent high barrier integrity marked by high transendothelial electrical resistance (TEER > 1500 Ω-cm2) and functional expression of drug efflux transporters. The radioiodinated an…
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analysis of cancer targeting Alkylphosphocholine analogue permeability characteristics using a human induced pluripotent stem cell blood brain barrier model
Molecular Pharmaceutics, 2016Co-Authors: Paul A. Clark, Ray R. Zhang, John S. Kuo, Jamey P. Weichert, Tongcheng Qian, Hannah K. Wilson, Sean P. Palecek, Abraham Alahmad, Eric V. ShustaAbstract:Cancer-targeting Alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure–activity studies. While they strongly label human brain cancers associated with disrupted blood–brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). This in vitro BBB system has reproducibly consistent high barrier integrity marked by high transendothelial electrical resistance (TEER > 1500 Ω-cm2) and functional expression of drug efflux transporters. The radioiodinated an…
Verena Jendrossek – One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics and biodistribution of Erufosine in nude mice – implications for combination with radiotherapy
Radiation oncology (London England), 2009Co-Authors: Guido Henke, Hansjörg Eibl, Lars H. Lindner, Michael Vogeser, Jürgen Wörner, Arndt Christian Müller, Michael Bamberg, Kirsten Wachholz, Claus Belka, Verena JendrossekAbstract:Background Alkylphosphocholines represent promising antineoplastic drugs that induce cell death in tumor cells by primary interaction with the cell membrane. Recently we could show that a combination of radiotherapy with Erufosine, a paradigmatic intravenously applicable Alkylphosphocholine, in vitro leads to a clear increase of irradiation-induced cell death. In view of a possible combination of Erufosine and radiotherapy in vivo we determined the pharmacokinetics and bioavailability as well as the tolerability of Erufosine in nude mice.
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Pharmacokinetics and biodistribution of Erufosine in nude mice – implications for combination with radiotherapy
Radiation Oncology, 2009Co-Authors: Guido Henke, Hansjörg Eibl, Lars H. Lindner, Michael Vogeser, Jürgen Wörner, Arndt Christian Müller, Michael Bamberg, Kirsten Wachholz, Claus Belka, Verena JendrossekAbstract:Background Alkylphosphocholines represent promising antineoplastic drugs that induce cell death in tumor cells by primary interaction with the cell membrane. Recently we could show that a combination of radiotherapy with Erufosine, a paradigmatic intravenously applicable Alkylphosphocholine, in vitro leads to a clear increase of irradiation-induced cell death. In view of a possible combination of Erufosine and radiotherapy in vivo we determined the pharmacokinetics and bioavailability as well as the tolerability of Erufosine in nude mice. Methods NMRI (nu/nu) nude mice were treated by intraperitoneal or subcutaneous injections of 5 to 40 mg/kg body weight Erufosine every 48 h for one to three weeks. Erufosine-concentrations were measured in brain, lungs, liver, small intestine, colon, spleen, kidney, stomach, adipoid tissue, and muscle by tandem-mass spectroscopy. Weight course, blood cell count and clinical chemistry were analyzed to evaluate general toxicity. Results Intraperitoneal injections were generally well tolerated in all dose groups but led to a transient loss of the bodyweight (
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The membrane targeted apoptosis modulators erucylphosphocholine and erucylphosphohomocholine increase the radiation response of human glioblastoma cell lines in vitro
Radiation Oncology, 2006Co-Authors: Amelie Rübel, Hansjörg Eibl, Lars H. Lindner, Claus Belka, René Handrick, Matthias Steiger, Wilfried Budach, Verena JendrossekAbstract:Background Alkylphosphocholines constitute a novel class of antineoplastic synthetic phospholipid derivatives that induce apoptosis of human tumor cell lines by targeting cellular membranes. We could recently show that the first intravenously applicable Alkylphosphocholine erucylphosphocholine (ErPC) is a potent inducer of apoptosis in highly resistant human astrocytoma/glioblastoma cell lines in vitro. ErPC was shown to cross the blood brain barrier upon repeated intravenous injections in rats and thus constitutes a promising candidate for glioblastoma therapy. Aim of the present study was to analyze putative beneficial effects of ErPC and its clinically more advanced derivative erucylphosphohomocholine (erucyl-N, N, N-trimethylpropanolaminphosphate, ErPC3, Erufosine™ on radiation-induced apoptosis and eradication of clonogenic tumor cells in human astrocytoma/glioblastoma cell lines in vitro.
Paul A. Clark – One of the best experts on this subject based on the ideXlab platform.
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Analysis of Cancer-Targeting Alkylphosphocholine Analogue Permeability Characteristics Using a Human Induced Pluripotent Stem Cell Blood–Brain Barrier Model
Molecular pharmaceutics, 2016Co-Authors: Paul A. Clark, Ray R. Zhang, John S. Kuo, Jamey P. Weichert, Abraham Al-ahmad, Tongcheng Qian, Hannah K. Wilson, Sean P. Palecek, Eric V. ShustaAbstract:Cancer-targeting Alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure–activity studies. While they strongly label human brain cancers associated with disrupted blood–brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). This in vitro BBB system has reproducibly consistent high barrier integrity marked by high transendothelial electrical resistance (TEER > 1500 Ω-cm2) and functional expression of drug efflux transporters. The radioiodinated an…
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analysis of cancer targeting Alkylphosphocholine analogue permeability characteristics using a human induced pluripotent stem cell blood brain barrier model
Molecular Pharmaceutics, 2016Co-Authors: Paul A. Clark, Ray R. Zhang, John S. Kuo, Jamey P. Weichert, Tongcheng Qian, Hannah K. Wilson, Sean P. Palecek, Abraham Alahmad, Eric V. ShustaAbstract:Cancer-targeting Alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure–activity studies. While they strongly label human brain cancers associated with disrupted blood–brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). This in vitro BBB system has reproducibly consistent high barrier integrity marked by high transendothelial electrical resistance (TEER > 1500 Ω-cm2) and functional expression of drug efflux transporters. The radioiodinated an…
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fluorescent cancer selective Alkylphosphocholine analogs for intraoperative glioma detection
Neurosurgery, 2015Co-Authors: Kyle I. Swanson, Ray R. Zhang, Jamey P. Weichert, Paul A. Clark, Irawati Kandela, Mohammed Farhoud, John S. KuoAbstract:BACKGROUND 5-Aminolevulinic acid (5-ALA)-induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of 2 novel fluorescent, cancer-selective Alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near infrared), in a proof-of-principle study for fluorescence-guided glioma surgery. OBJECTIVE To demonstrate that CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and to compare tumor-to-normal brain (T:N) fluorescence ratios with 5-ALA. METHODS CLR1501, CLR1502, and 5-ALA were administered to mice with magnetic resonance imaging-verified orthotopic U251 glioblastoma multiforme- and glioblastoma stem cell-derived xenografts. Harvested brains were imaged with confocal microscopy (CLR1501), the IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or the Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed. RESULTS Excitation/emission peaks are 500/517 nm for CLR1501 and 760/778 nm for CLR1502. The observed T:N ratio for CLR1502 (9.28±1.08) was significantly higher (P<.01) than for CLR1501 (3.51±0.44 on confocal imaging; 7.23±1.63 on IVIS imaging) and 5-ALA (4.81±0.92). Near-infrared Fluobeam CLR1502 imaging in a mouse xenograft model demonstrated high- contrast tumor visualization compatible with surgical applications. CONCLUSION CLR1501 (green) and CLR1502 (near infrared) are novel tumor-selective fluorescent agents for discriminating tumor from normal brain. CLR1501 exhibits a tumor-to-brain fluorescence ratio similar to that of 5-ALA, whereas CLR1502 has a superior tumor-to-brain fluorescence ratio. This study demonstrates the potential use of CLR1501 and CLR1502 in fluorescence-guided tumor surgery.