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.