Preclinical Evaluation of DO3A-Act-AQ: A Polyazamacrocyclic Monomeric Anthraquinone Derivative as a Theranostic Agent

An anthraquinone conjugated macrocyclic chelating agent, 2,2′,2″-(10-(2-(9,10-dioxo-9,10-dihydroanthracen-1-ylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid or DO3A-Act-AQ, was synthesized by reacting trisubstituted cyclen (DO3A) with 2-chloro-N-(9,10-dioxo-9,10-dihydro-anthracen-1-yl)-acetamide and radiolabeled with 68GaCl3 in 84% efficiency and a specific activity of 4.62 MBq/nmol. The IC50 value for BMG-1 cells was 0.1 mM, while the same concentration of DO3A-Act-AQ rendered no significant toxicity in HEK cells. The exposure of BMG-1 cells with 0.1 mM DO3A-Act-AQ displayed a time-dependent increase in apoptosis (40.7% at 4 h and 53% at 24 h), and the effect was 2.8- and 3.6-fold % higher as seen in HEK cells. An increase in S-phase cell population suggested S-phase arrest concomitant with induction of apoptosis in BMG-1 cells reaching to 4.5 times after 24 h with respect to control cells. DNA binding studies on CT-DNA (calf thymus) revealed a quenching pattern in the prese...