New issues for copper-64: from precursor to innovative PET tracers in clinical oncology.

The role of copper in the metabolism of human cancer cells has been largely investigated in the last 20 years and a strong relationship between copper levels and cancer progression has been demonstrated. Moreover copper is involved in tumor angiogenesis as well as in non-neoplastic conditions like neurodegenerative diseases. The main mechanism of action is related to a cellular transporter (CTR1) that plays a pivotal role in preserving the intra-cellular homeostasis, allowing at the same time the anti- tumor activity of platinum based therapies. Copper-64, emitting positrons and β- radiations, is suitable for the labeling of a large number of molecules that could be used for radionuclide imaging, being also usable in radionuclide therapy. Nevertheless few data are at present available on radiotracers labeled with radiocopper and in particular on the use of (64)Cu-Cl2 in cancer patients. In this paper we analyze the potential applications for Copper-64 as PET agent in the clinical oncological scenario.