High Cytotoxic Effect by Combining Copper-64 with a NOTA–Terpyridine Platinum Conjugate

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 (64Cu), 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 [64Cu]­Cu–1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)–TP is stable, permitting selective killing of cancer cells. The antitumor activity of [64Cu]­Cu–NOTA–TP at high apparent molar activity is in the low nanomolar range and 27,800-fold greater than that of natCu–NOTA–TP at 24 h post treatment. These results suggest that this combination of a cytotoxic TP agent with 64Cu has considerable potential for cancer treatment and PET imaging.