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A Bivalent Inhibitor of Prostate Specific Membrane Antigen Radiolabeled with Copper‐64 with High Tumor Uptake and Retention
Author(s) -
Zia Nicholas A.,
Cullinane Carleen,
Van Zuylekom Jessica K.,
Waldeck Kelly,
McInnes Lachlan E.,
Buncic Gojko,
Haskali Mohammad B.,
Roselt Peter D.,
Hicks Rodney J.,
Donnelly Paul S.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201908964
Subject(s) - bivalent (engine) , chemistry , prostate cancer , linker , glutamate carboxypeptidase ii , prostate , copper , lysine , monomer , cancer research , biophysics , combinatorial chemistry , biochemistry , cancer , medicine , amino acid , polymer , biology , organic chemistry , computer science , metal , operating system
Molecules containing lysine‐ureido‐glutamate functional groups bind to the active site of prostate specific membrane antigen, which is overexpressed in prostate cancer. To prepare copper radiopharmaceuticals for the diagnosis and therapy of prostate cancer, macrobicyclic sarcophagine ligands tethered to either one or two lysine‐ureido‐glutamate functional groups through an appropriate linker have been prepared. Sarcophagine ligands can be readily radiolabeled with positron‐emitting copper‐64 at room temperature. The bivalent agent, in which two targeting groups are tethered to a single copper complex, dramatically outperforms the monomeric agent with respect to tumor uptake and retention. The high tumor uptake, low background, and prolonged tumor retention, even at 24 hours post injection, suggest the bivalent agent is a promising diagnostic for prostate cancer and could be used for prospective dosimetry for therapy with a copper‐67 variant.