A 64Cu(II)-based radiotracer for diagnosing hypoxic conditions in cancer cells

Objectif

Cancer is a leading cause of morbidity and mortality worldwide, development of new methodologies to early and accurate diagnosis of cancer, should reduce these death rates. Hypoxia is associated with low oxygen levels in the cells, which leads to an increase in tumor aggressiveness, and to resistance to chemotherapy and radiation therapy. Therefore, there is a compelling need to develop a biomarker for detection and imaging of hypoxic cells. Despite on-going efforts to identify and/or track hypoxia, there is still no routinely used clinical biomarker or a radiotracer of hypoxia.
In the framework of the ERC-Stg CuHypMech project, we succeeded in developing a suitable, highly selective and sensitive radiotracer based on 64Cu(II) for PET-CT/PET-MRI imaging to report on the hypoxic conditions of cells. This was achieved by monitoring the cellular copper transfer mechanism in human breast cancer cells, specifically by identifying the various copper-binding sites in those proteins involved and identifying factors critical for proper copper transfer. Based on this molecular-level insight into cellular pathways involving copper, a lead compound was designed and characterized and termed 64CuCysPhe.
Our lead 64CuCysPhe compound showed promising in vitro and in vivo results in breast cancer models. In this PoC proposal, we would like to expand our in vivo experiments by testing our compound in additional cancers, such as cervical and prostate cancers. The main objective of this proposal is to complete all pre-clinic experiments needed before entering the clinic. This will require us to show good identification of the tumor in various tumors of varied sizes from different cancers. We will also have to correlate imaging intensity with hypoxia levels. Finally, we will have to find ways to reduce preparation costs of our compound and seek subsequent investments (either non-dilutive through EIC Transition, or dilutive through business angels or venture capital funds).