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Meeting ReportOncology: Basic, Translational & Therapy

Anti-PSMA labeled liposomes loaded with Actinium-225 for potential antivascular alpha-radiotherapy

Charles Zhu, Amey Bandekar, Sangeeta Ray, Martin Pomper, Frank Bruchertseifer, Alfred Morgenstern and Stavroula Sofou
Journal of Nuclear Medicine May 2014, 55 (supplement 1) 640;
Charles Zhu
1Rutgers University, Piscataway, NJ
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Amey Bandekar
1Rutgers University, Piscataway, NJ
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Sangeeta Ray
2Johns Hopkins Medical School, Baltimore, MD
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Martin Pomper
2Johns Hopkins Medical School, Baltimore, MD
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Frank Bruchertseifer
3Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe, Germany
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Alfred Morgenstern
3Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe, Germany
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Stavroula Sofou
1Rutgers University, Piscataway, NJ
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Abstract

640

Objectives We studied targeted liposomes loaded with the alpha-particle generator actinium-225 (225Ac) to kill cells expressing the prostate-specific-membrane-antigen (PSMA) with the overall goal of evaluating the potential of these liposomes for targeted antivascular alpha-radiotherapy. The targeting moiety is designed to bind PSMA, which is unique to human neovasculature for a variety of solid tumors. The therapeutic radionuclide 225Ac emits a total of four alpha-particles per decay, providing highly lethal and localized irradiation of targeted cells with minimal exposure of surrounding healthy tissues. Finally, the delivery vehicle, a liposome, can be loaded with substantial levels of radioactivity and can be engineered for rapid clearance to shift the distribution away from the kidneys, the dose-limiting organ, and toward the spleen and liver.

Methods Liposomes were labeled with two types of PSMA-targeting ligands: a fully human PSMA antibody (mAb), and a urea-based low-molecular-weight agent. Targeting selectivity, extent of internalization and killing efficacy were evaluated on monolayers of LNCaP cells intrinsically expressing PSMA and on monolayers of HUVEC induced to express PSMA in static incubation conditions and under flow at a 15s-1 shear rate in a parallel-plate flow chamber.

Results Specific cell association increases with incubation time and decreases by twofold upon introduction of flow. Both types of radiolabeled PSMA-targeting liposomes exhibited similar killing efficacy, which was greater than the efficacy of the radiolabeled control mAb. Fluorescence confocal microscopy demonstrated that targeted liposomes localized near the nucleus, unlike antibodies which localized near the plasma membrane, suggesting that perinuclear localization may enhance the probability of alpha-particle trajectories crossing the nuclei.

Conclusions These findings suggest the potential of PSMA-targeting liposomes.

Research Support Supported by the American Cancer Society Grant RSG-12-044-01 and in part by the National Science Foundation Grant DMR1207022 and the Charles and Johanna Busch Memorial Fund.

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Journal of Nuclear Medicine
Vol. 55, Issue supplement 1
May 2014
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Anti-PSMA labeled liposomes loaded with Actinium-225 for potential antivascular alpha-radiotherapy
Charles Zhu, Amey Bandekar, Sangeeta Ray, Martin Pomper, Frank Bruchertseifer, Alfred Morgenstern, Stavroula Sofou
Journal of Nuclear Medicine May 2014, 55 (supplement 1) 640;

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Anti-PSMA labeled liposomes loaded with Actinium-225 for potential antivascular alpha-radiotherapy
Charles Zhu, Amey Bandekar, Sangeeta Ray, Martin Pomper, Frank Bruchertseifer, Alfred Morgenstern, Stavroula Sofou
Journal of Nuclear Medicine May 2014, 55 (supplement 1) 640;
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