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Bioconjugated chelates based on (methylpyridinyl)tacn: synthesis, 64Cu labeling and in vitro evaluation for prostate cancer targeting. | LitMetric

AI Article Synopsis

Article Abstract

Three new bifunctional copper chelators based on the 1,4,7-triazacyclononane (tacn) platform have been synthesized and conjugated to peptides. The first one is constituted of the tacn with two methylpyridinyl and one methylthiazolyl carboxylic acid pendant arms, while, in the second and third ones, the macrocycle is functionalized by three methylpyridinyl groups, with an additional hexynoic acid chain on a carbon of one or two pyridine rings. These three bifunctional chelators have been conjugated to the antagonist DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 peptide for targeting the gastrin-releasing peptide receptor, which is overexpressed in prostate cancer. The resulting monomeric bioconjugates have shown their efficiency to be radiolabeled with β+ emitter 64Cu, and the hydrophilicity and PC-3 cell internalization properties of these radiolabeled conjugates have been studied. PC-3 cell binding affinity of mono- and dimeric metal-free and natCu metallated conjugates have been evaluated by IC50 measurements. The results demonstrate the potential of these methylpyridinyl tacn derivatives for radiopharmaceutical applications.

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Source
http://dx.doi.org/10.1093/mtomcs/mfac036DOI Listing

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