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

Introduction

Cancer is a leading cause of morbidity and mortality worldwide. The development of new methodologies for 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 resistance to chemotherapy and radiation therapy. Therefore, there is a compelling need to develop a biomarker for the detection and imaging of hypoxic cells.

Current Challenges

Despite ongoing efforts to identify and/or track hypoxia, there is still no routinely used clinical biomarker or a radiotracer of hypoxia.

Project Overview

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:

1. Monitoring the cellular copper transfer mechanism in human breast cancer cells.
2. Identifying the various copper-binding sites in the proteins involved.
3. Identifying factors critical for proper copper transfer.

Based on this molecular-level insight into cellular pathways involving copper, a lead compound was designed, characterized, and termed 64CuCysPhe.

Results

Our lead 64CuCysPhe compound showed promising in vitro and in vivo results in breast cancer models.

Future Plans

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.

Objectives

The main objectives of this proposal are to:

1. Complete all pre-clinic experiments needed before entering the clinic.
2. Show good identification of the tumor in various tumors of varied sizes from different cancers.
3. Correlate imaging intensity with hypoxia levels.
4. Find ways to reduce preparation costs of our compound.
5. Seek subsequent investments, either non-dilutive through EIC Transition or dilutive through business angels or venture capital funds.