Abstract
A new study shows that MRI scanners can direct magnetically labeled macrophages bearing an oncolytic virus toward primary and metastatic tumors in mice. Researchers hope this approach, called magnetic resonance targeting, can be scaled for use in humans, to improve the delivery of cell-based cancer therapy.
MRI is best known for its role in tumor diagnosis and staging, but new research suggests that it's useful for more than capturing detailed images of a patient's cancer. According to a recent study, MRI scanners can steer macrophages carrying an oncolytic virus (OV) directly toward tumors—an approach called magnetic resonance targeting (MRT).
Macrophages, a type of white blood cell, are “a good delivery vehicle for OVs because they have a particular fondness for tumors and protect the virus from potentially neutralizing antibodies in the circulation,” explains the study's corresponding author Munitta Muthana, PhD, an immunobiologist at the University of Sheffield, UK. “However, these cells are often sequestered by other organs or trapped in the capillaries en route. So, we decided to make use of magnetic labeling, along with the powerful magnets found in MRI scanners, to improve their ability to reach tumor sites.”
Muthana and her colleagues began testing MRT in mice with primary prostate tumors and lung metastases. Ten mice, divided into two groups of five, were given macrophages labeled with super-paramagnetic iron oxide (SPIO) nanoparticles; each group was then placed in an MRI scanner. In one group, the researchers focused the gradient of the scanner's magnetic field so it was strongest around the primary tumors, and found that this drew large numbers of SPIO-loaded macrophages in that direction, resulting in a tumor infiltration rate of 42%. In contrast, in the second group—exposed to a static, unfocused magnetic field instead of MRT—only 7% of macrophages successfully reached prostate tumors. When the scanner's magnet was redirected to focus on metastatic lung tumors, the macrophage uptake with MRT was 18%, compared to 4% via natural cell trafficking in the non-MRT group.
Next, the researchers assessed the therapeutic benefit of MRT in their mouse model, using it to direct SPIO-loaded macrophages armed with the OV Seprehvir (Virttu Biologics), a genetically modified herpes simplex virus-1. With MRT, the rate of virus-induced tumor necrosis increased by about 30%, primary prostate tumors shrank significantly, and lung metastases were reduced by about 80%. This was likely “the first time an MRI scanner has been used to deliver a cell-based therapy,” Muthana notes.
This study “confirms that magnetic field gradients within a preclinical MRI system are able to control, to some degree, the targeting of SPIO-loaded cells,” says co-author Jon Dobson, PhD, a professor of biomedical engineering at the University of Florida in Gainesville, who helped originate the concept of using magnetic nanoparticles to improve macrophage trafficking to tumors. Importantly, Dobson adds, magnetic forces similar to that used in this study can be produced in the clinic, so MRT is translationally feasible.
Muthana plans to carry out mathematical modeling to scale MRT for human use, and to predict its efficacy in other cancer types, including brain tumors. Minimizing the time patients would spend in the scanner—while still achieving the same therapeutic benefit—is another goal.
“The beauty of this drug delivery approach is that MRI scanners can also provide real-time imaging that tracks administered therapy,” she says, “and simply changing the direction of the magnetic field may enable us to target multiple tumors in a single round.”
