A new radio-imaging, diagnostic agent to guide targeted therapy for epithelial ovarian cancer 

Professor John Hooper and his team are investigating improving ovarian cancer outcomes with a theranostics approach — precision medicine that combines accurate diagnostics and targeted treatment into the same approach.  

The imaging formula they are testing uses safe doses of radioactive particles that could improve the effectiveness of Positron Emission Tomography (PET) scanning techniques, better displaying cancer presence and location to enable targeted treatments, or assist surgeons to visualise cancer prior to operations. 

Professor Hooper has been researching this approach for over two decades. The spark began during his postdoctoral studies in the United States where the lab he was working in had identified a series of antibodies — tiny molecules that were binding to proteins on the surface of cancer cells and helping them to grow. If they could work out what those antibodies were actually binding to on the cancer cell surface, maybe they could stop this binding from occurring, and subsequently stop the cancer progressing.  

His colleagues didn’t know how to confirm what on the surface of cells enabled the antibody binding. However, thanks to his experience in innovative bioinformatics and proteomics techniques, Professor Hooper did. He identified a protein called CDCP1 on the cancer cell surface, which plays a role in cancer growth and spread. He then focused on developing a second antibody that was able to stop CDCP1 — called 10D7. 

With OCRF and Medical Research Future Fund funding, the team are testing their new radio-imaging agent to see how effectively it firstly allows them to visualise specific ovarian cancer cells in preclinical models, then, if cancer presence is confirmed, test the effectiveness of an injected, second formula designed for treatment.   

The team aim to: 

• Test their formula for diagnostics and therapy in preclinical models, including testing a library of novel theranostic formulas for epithelial ovarian cancers, including high-grade serous ovarian cancer which is the most common and aggressive subtype. 
• Validate the performance and safety of the formulas, including the radioactive particles involved, and prepare it for a first-in-human study.  

First the team need to identify how commonly the CDCP1 protein is present on patient tumours, using immunohistochemistry techniques, to confirm whether targeting it will stop cancer in many patients. 

Secondly, they need to test, in ovarian cancer cell lines, how well the antibody can directly target CDCP1, and also test how strongly it binds to the CDCP1 on the cancer cells. This will help them understand whether the treatment can selectively target ovarian cancer cells, or if it is also targeting healthy cells which can lead to side effects. 

On a molecular level, the diagnostic formula works like this:  

• CDCP1 is the protein on the surface of the cancer cells. 
• 10D7 is the antibody Professor Hooper identified that can stop the cancer-causing functions of CDCP1. 
• Zirconium-89 is the radioactive particle attached to 10D7, which then binds to CDCP1, allowing PET scans to visualise the cancer. 

The team will engineer the 10D7 antibody, attaching it to the Zirconium particles, so that 10D7 ‘docks’ or binds to the Zirconium. The engineered particles will then be injected into sophisticated preclinical models that mimic a human tumour environment, moving through blood circulation until they find cancer cells with the CDCP1 protein on the surface. The Zirconium particle then gives off a signal that’s detected by a PET scanner, allowing clinicians to understand if cancer is present, and if so, where it has spread to.  

The team are also confirming that the radioactive particle Zirconium-89 only emits a safe amount of energy so that the PET scanner can detect it while ensuring safety for human use.