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    177Lu radiolabeled peptides for breast cancer therapy [abstract]

    Calzada, Victoria
    Zhang, Xiuli
    Cabral, Pablo
    Fernandez, Marcelo
    Gambini, Juan Pablo
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    [PDF] 177LuRadiolabeledPeptides.pdf (223.5Kb)
    Date
    2010
    Contributor
    University of Missouri--Columbia. School of Medicine
    Format
    Abstract
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    Abstract
    ErbB-2 is a type 1 receptor tyrosine kinase over-expressed on ~30% of breast cancers and is an attractive target for the development of new diagnostic and therapeutic agents. The ErbB-2 avid peptide KCCYSL, originally identified from phage display, has shown promising imaging results in pre-clincial breast carcinoma animal models. In this study the peptide DOTA-GSGKCCYSL was radiolabeled with the beta-particle emitter lutetium-177 (177Lu) and examined for its therapeutic potential. The peptide DOTA-GSG-KCCYSL was synthesized using Fmoc solid phase peptide synthesis and purified to homogeneity. DOTA-GSG-KCCYSL was radiolabeled with Lu-177 and purified via high performance liquid chromatography. In vitro stability studies showed that the radiolabeled complex was stable to challenges from metal chelators and was stable to >60% in serum at 37[degrees]C over 24 h. Cell binding of 177Lu-DOTA-GSG-KCCYSL to MB- 435 human breast carcinoma cells displayed saturable binding at 2 h. Log P studies indicated that the radiolabeled complex was very hydrophilic. Initial biodistribution studies in MB-435 xenografted mice showed modest tumor uptake of 1.82 % injected dose per gram (ID/g) 30 min post injection and 0.56 % ID/g at 1 h post injection. Additional biodistribution and imaging studies are underway to determine dosimetry and potential tumor therapeutic properties.
    URI
    http://hdl.handle.net/10355/9144
    Rights
    OpenAccess.
    This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
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