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High Cytotoxic Effect by Combining Copper-64 with a NOTA-Terpyridine Platinum Conjugate. | LitMetric
Terpyridine platinum (TP)-based chemotherapeutic agents target three-dimensional structures on DNA known as G-quadruplexes. We report the rational design and synthesis of a TP conjugate combined with copper-64 (Cu), the decay characteristics of which include emission of β and Auger electrons for radiotherapy and β particles for positron emission tomography (PET) imaging. The present experimental studies show that the novel [Cu]Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-TP is stable, permitting selective killing of cancer cells. The antitumor activity of [Cu]Cu-NOTA-TP at high apparent molar activity is in the low nanomolar range and 27,800-fold greater than that of Cu-NOTA-TP at 24 h post treatment. These results suggest that this combination of a cytotoxic TP agent with Cu has considerable potential for cancer treatment and PET imaging.
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