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CuTira Brachytherapy: A New Combination of Radioactive Copper Isotopes and the Hypoxic Cytotoxin, Tirapazamine, for Targeted Tumor Therapy

Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia

Correspondence: For correspondence or reprints contact: Peck-Sun Lin, PhD, Department of Radiation Oncology, Medical College of Virginia, Richmond, VA 23298.

ABSTRACT

We previously showed a significant enhancement of tirapazamine-induced cytotoxicity and DNA damage after binding with copper. This result suggests that conjugates of tirapazamine with radioactive copper, i.e., ⁶⁴Cu and ⁶⁷Cu, may offer potential for targeted therapy of a wide range of advanced stage tumors including a possibile treatment for patients with solitary hepatocellular carcinoma by intrahepatic arterial infusion. Major supporting considerations include: (a) tirapazamine having a high selective toxicity against hypoxic cells; (b) the nature of radioactive decay of these copper isotopes and obtainable high specific activity; and (c) simple procedure for the production of copper-tirapazamine complex.

Key Words: copper isotopes • hypoxic cytotoxin, tirapazamine, tumor therapy