Novel ⁶⁴ Cu(II) Radiotracer for diagnoses of hypoxic conditions based on the cellular copper cycle

Cancer is a disease characterized by uncontrolled cellular proliferation. Accumulation of the abnormal cells creates a tumor that can in some cases migrate throughout the body producing metastases. Cancer cells contain genetic mutations which are often the result of; hereditary, hormonal, physical, viral, bacterial factors, immune system dysfunction, carcinogens, ionizing radiation and more. Treating cancer is difficult as it may return even after treatment and in late stages of disease the cancer cells develop resistance, often because of the increased rate of proliferation leading to the formation of new genetic mutations. Therefore, early detection is of importance, allowing a stronger chance of cure. With the help of early detection, it will be possible to adapt the treatment to the person and the condition of their illness. Tumors are characterized by hypoxic conditions, which also lead to aggressive phenotypes. Today, in order to characterize tumors, an invasive biopsy is required. Therefore, there is an urgent need to develop biomarkers that will be able to quantitatively characterize the tumor’s state. In this study, we are developing a new radiotracer for hypoxic cells based on the copper oxidation-reduction process in the cells and the cellular copper metabolism. We succeeded to design a compound that it is highly selective to hypoxia conditions, and it is highly uptake by different cancer cells. This was achieved by first characterizing the copper cellular mechanism using various spectroscopic techniques. We present new results including, in-vitro and in-vivo PET-MRI on various cancer models.