A novel technology designed to precisely image aggressive brain cancers and guide treatment is being prepared for a phase 1 trial in glioblastoma, the most common type of brain cancer. The new MRI nanotechnology targets a specific marker, fibroblast activation protein (FAP), that is found in the majority of solid tumors, including high-grade brain cancers. The tool is being developed by the University of South Australia (UniSA) and Australian cancer diagnostic company, Ferronova.
This new agent will be particularly useful in, “Tumors where precision treatment is needed, for example brain tumors where very aggressive treatment can dramatically impact the quality of life of survivors. Better imaging of these cancers is expected to enable aggressive tumor targeting, for example with radiation, while sparing non-cancerous brain tissues,” UniSA’s Nicole Dmochowska told Inside Precision Oncology. She will lead the research.
FAB is a transmembrane protein overexpressed in stromal tumoural components in more than 90% of epithelial cancers including many tumors located in the brain, breast, and gastrointestinal organs. The expression of FAP often correlates with disease prognosis and is very specific to tumor tissues. As such, Dmochowska told IPO, “It has been gaining momentum as a ‘pan-cancer’ marker and is often suggested as having the potential to induce paradigm shifts in cancer imaging.”
Glioblastoma affects about 3.2 people per 100,000 each year, and has a 5 year survival rate of only 5-10%. In 2021, there were 1896 brain cancers (1191 males and 725 females) in Australia alone.
The agent has already yielded promising preclinical results in a prostate cancer model. Successful outcomes in this glioblastoma pilot would lead to other trials for example aimed at improving the treatment of childhood brain cancer.
Dmochowska says there is a critical need for better imaging of high-grade brain tumors. “The prognosis for high-grade brain tumors such as glioblastoma remains abysmal, so it’s vital that we progress new technologies that can potentially enable more precise targeting of tumors.”
MRI neuronavigation is critical in the treatment of brain tumors, for determining tumor structure/border and biology, for guiding surgical resection, as well as image-guided radiotherapy. Additionally, techniques such as functional MRI and tractography are used to define important brain cortices and tracts, with the aim of minimizing postsurgical neuro-deficits.
Hien Le, a radiation oncologist at the Royal Adelaide Hospital and one of the Chief Investigators in the seed funding for this work, says the research has potential to advance cancer treatments.
“As someone who specializes in the management of brain cancer, I understand the importance of accurate tumor delineation,” Le says “Better imaging means we can more confidently define the tumor target, facilitating precise treatment delivery, whilst minimizing damage to normal healthy tissues.”
Melanie Nelson, R&D Manager at Ferronova, says the research will streamline preclinical validations for the technology for brain tumors, in preparation for a phase 1 clinical trial.
FerroTrace-FAPi is based on modification of first generation FerroTrace, which is an MRI precision surgery nanoparticulate agent undergoing clinical trials in head and neck, colorectal, gastric and breast cancer. The binding of these particles is guided to the tumor by a FAP targeting ligand developed by a collaborator at Purdue University, Professor Phil Low. These nanoparticles contain an iron core with a precisely controlled oxidation level and are designed to induce a strong contrast in the tumor on MRI, giving clinicians a more accurate depiction of the tumor’s boundaries.