The Cytotoxic Effect of 64Cu/NOTA-Terpyridine Platinum Conjugate, as a Novel Chemoradiotherapy Agent

Colorectal cancer is one of the most prevalent cancers worldwide that displays both intrinsic and acquired resistance to platinum-based chemotherapeutic agents (Pt-CAs). To overcome such resistance, new classes Pt-CAs have been proposed, including terpyridine (TP) compounds target G-quadruplex tertiary structure DNA. Additionally, recent studies indicate a maximum chemoradiation benefit when radiation administered with at their highest concentrations in cell Accordingly, we synthesized novel chemo-radiotheranostic agent by conjugating TP moiety 64Cu (64Cu-NOTA-TP). The vitro cytotoxic effects, cellular uptake, internalization efflux 64Cu-NOTA-TP were measured for colorectal (HCT116) normal fibroblast (GM05757) cells. Radiolabeling NOTA-TP resulted 17,530-, 40,083- 66,000-fold enhancements its cytotoxicity against HCT116 cells (EC50 = 0.017 ± 0.004, 0.012 0.006 0.005 0.0002 µM) as compared coldCu-NOTA-terpyridine 298 2, 481 25 330 51 24, 48 72 h post-administration, respectively. More importantly, 64Cu-conjugate toward was about 3.8-fold higher than GM05757 24 h. This result consistent 2–3-fold relative similar times. internalized activity steadily increased from 0.04 0.02% 18.7 2.8% over incubation time. Moreover, kinetics showed more 40% retained period. In conclusion, this work presents chemo-radiotherapeutic considerable potential targeted treatment combined radioisotope imaging.