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A multivalent approach of imaging probe design to overcome an endogenous anion binding competition for noninvasive assessment of prostate specific membrane antigen
Guiyang Hao; Amit Kumar; Timothy Dobin; Orhan K. Öz; Jer-Tsong Hsieh; Xiankai Sun(Profiled Authors: Guiyang Hao; Jer-Tsong Hsieh; Xiankai Sun)
Molecular Pharmaceutics. 2013;10(8):2975-2985.Abstract
2[(3-Amino-3-carboxypropyl)(hydroxy)(phosphinyl)methyl]pentane-1,5-dioic acid) (GPI) is a highly potent inhibitor of prostate specific membrane antigen (PSMA) with a rapid in vivo clearance profile from nontarget organs including kidneys, but its use for imaging of PSMA is impeded by an endogenous anion (serum phosphate) competition, which compromises its specific binding to the antigen. Multipresentation of a targeting molecule on a single entity has been recognized as a practical way for imaging sensitivity enhancement. Herein, we demonstrate a multivalent approach based on a 64Cu-specific bifunctional chelator scaffold to overcome the endogenous phosphate competition thus enabling the utility of GPI conjugates for in vivo detection of PSMA and imaging quantification. Both monomeric (H
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