New imaging method helps immune cells zero in on cancer

To understand the University of Florida’s nanoparticle imaging research and its potential to boost cancer immunity, think of bloodhounds sniffing out troubled targets.  

White blood cells (T cells) are the bloodhounds. Cancer is the trouble. And dendritic cell therapy is the trainer directing those bloodhounds to those targets.   

Now, in a collaboration between UF’s biomedical engineering and neurosurgery departments, UF researchers are testing nanoparticle imaging to track that process and make sure T cells get to those cancer cells. 

Dendritic cells are immune cells from patients’ blood or lymph nodes, processed to recognize cancer-specific antigens and then injected back into patients to fight cancer cells and stimulate the immune system. The therapy’s efficacy is being examined in combination with immunotherapy clinical trials at the Preston A. Wells Jr., Center for Brain Tumor Therapy at UF Health.

Two UF researchers want to know why some patients respond to dendritic cell therapy and some do not. Now armed with a $2.6 million grant from the National Institutes of Health (NIH) and a rare nanoparticle imaging machine, they intend to find out. 

This research promises to advance immunotherapy by tracking the migration of dendritic cells with innovative nanoparticle imaging. Traditional imaging, such as PET scans, have drawbacks, including toxicity to the dendritic cells.

“Reliable imaging is needed, and magnetic nanoparticles are non-invasive and exclude radiative treatments,” said Professor Carlos Rinaldi-Ramos, Ph.D., who specializes in biomedical applications of these nanoparticles.

Rinaldi-Ramos serves as the project’s co-principal investigator alongside Duane Mitchell, M.D., Ph.D., the Phyllis Kottler Friedman Professor in UF's Department of Neurosurgery and co-director of the Wells Brain Tumor Center at UF Health.

“We want to replace radioactive imaging agents with nanoparticles,” Rinaldi-Ramos said.

Accurately tracking injected dendritic cells though imaging is important to see if the treatment gets to the lymph nodes, which increases effectiveness of the cell therapy and has been associated with improved survival rates.

“Lymph nodes are immune organs where dendritic cells ‘talk' to T cells, giving them direction to go out and find the cancer cells and destroy them,” Rinaldi-Ramos said. “If they don't get to the right location, they don't work.”

The team, he said, is developing imaging technology to track the migration of those dendritic cells to lymph nodes to predict therapy response and help develop more effective dendritic cell therapies.  

This research falls in line with UF Health’s longtime focus on the advancing cellular immunotherapy treatments, particularly for malignant brain tumors in children and adults.

“We have translated many cell therapy approaches using dendritic cells and other immune cells, like T cells, into therapeutic interventions in patients, and we’ve seen very encouraging results using cell therapies to treat very difficult cancers,” Mitchell said.  

But, he added, there are no reliable ways of following the migration of these immune cells in the body and, thus, knowing if they are reaching their targets. 

“How effectively are they getting to the sites we need these immune cells to get to in order to carry out their activity? This has been an area of great interest and importance, not just for our own work but for the field of cell therapy in general,” Mitchell said.  

UF, therefore, is “well-positioned to lead nationally and globally” in using this technology to make these therapies effective for more patients, Mitchell added. 

Central to the research is UF's Magnetic Particle Imaging (MPI) technology, a scanner made by Magnetic Insight with unparalleled precision in tracking nanoparticles in the body.  Currently, MPI research is conducted with mice.   

“Longer term, I hope to get the support to have UF be the home of the first — if not one of the first — whole-body MPI scanners,” Rinaldi-Ramos said.   

Using the scanner as a non-invasive, quantitative way to track immune cells may help inform designing better vaccines, Rinaldi-Ramos added.  

“If it's an immunotherapy, the more lymph nodes you hit, the more effective it might be,” he said. “And so this allows us to study how the properties of the particles can influence how deep they penetrate, how many they reach, how many particles were retained."  

UF’s MPI nanoparticle scanner was installed in 2019 with funds provided by the Herbert Wertheim College of Engineering and the department of Biomedical Engineering. In 2021, Rinaldi-Ramos received two grants to develop nanoparticles to study cell tracking and cancer therapy with the scanner.  

This new project is a direct result of UF’s early investment in the scanner hardware and initial support from the UF Health Cancer Center and the NIH. 

“We think there's tremendous potential for MPI to be an early, non-invasive imaging biomarker of response to cellular immunotherapy," Mitchell said. “For the whole field of cellular therapy for cancer, being able to non-invasively image and quantitatively image cell trafficking is a significant and unmet need.  This study may pave the way toward providing a solution.”