CUTIRA BRACHYTHERAPY - A NEW COMBINATION OF RADIOACTIVE COPPER ISOTOPES AND THE HYPOXIC CYTOTOXIN, TIRAPAZAMINE, FOR TARGETED TUMOR-THERAPY

We previously showed a significant enhancement of tirapazamine-induced cytotoxicity and DNA damage after binding with copper. This result su ggests that conjugates of tirapazamine with radioactive copper, i.e., (CU)-C-64 and (CU)-C-67, may offer potential for targeted therapy of a wide range of advanced stage tumors including a possible treatment fo r patients with solitary hepatocellular carcinoma by intrahepatic arte rial infusion. Major supporting considerations include: (a) tirapazami ne having a high selective toxicity against hypoxic cells; (b) the nat ure of radioactive decay of these copper isotopes and obtainable high specific activity, and (c) simple procedure for the production of copp er-tirapazamine complex.