Clockwise from top left:
A tumor is heated with ultrasound;
heat map of tumor during treatment;
PET scan shows nanoparticles in surviving
tumor margin; bright contrast
agent shows area damaged by heat.
Courtesy of Andrew Wong

MR-guided focused ultrasound plus chemo cures tumors in mice

December 08, 2015
by Lauren Dubinsky, Senior Reporter
A technique that combines MR-guided focused ultrasound surgery (MRgFUS) and chemotherapy has shown promise in curing tumors in mice, according to new research from UC Davis. A paper discussing the research was published in The Journal of Clinical Investigation.

MRgFUS is a noninvasive procedure that involves an ultrasound beam that heats and destroys tissue, and an MR system to guide the beam and monitor the effects of treatment. It’s already FDA approved for the treatment of uterine fibroids and palliation of bone metastases, but the researchers hope that its indication will expand by supplementing it with chemotherapy.

“There is a great deal of work going on in tailoring MRgFUS to specific organs and there are challenges,” Katherine W. Ferrara, professor of biomedical engineering at UC Davis, told HCB News. “For example, the motion of the liver and the higher perfusion of the kidney must be accounted for. Still, we are very optimistic as to the future of using this technique in various cancers.”

When the UC Davis researchers combined MRgFUS and chemotherapy they found that it can destroy a whole tumor without thermal destruction of the tumor margin. They also found a significant increase in the amount of anti-cancer chemotherapy within several types of MRgFUS thermal ablation-treated tumors.

In Ferrara’s previous research she found that ultrasound-induced mild hyperthermia can improve the accumulation of tiny nanoparticles that transport anti-cancer drugs, but the degree of accumulation depends on the type of tumor. The team thinks that combining thermal ablation with chemotherapy could improve the accumulation across various types of tumors.

The researchers used different techniques including PET/CT, MR, autoradiography and fluorescence imaging to track nanoparticles filled with the chemotherapy drug, doxorubicin, in a mouse with breast cancer. They uncovered that the ultrasound damaged the tumor and induced a local immune response so that the nanoparticles accumulated in the tumor and increased the drug concentration 50-fold.

In addition, the high drug concentrations remained over several weeks, which increased the tumor’s total exposure to the drug. The researchers concluded that MRgFUS improved drug accumulation and resulted in improved survival and a consistent cure in their preclinical trial for breast cancer, even when part of the tumor was left intact.

They also showed that a carefully designed protocol that involves heat-activated nanoparticles that are gently heated by ultrasound and release the chemotherapy drugs in the vascular system surrounding the tumor is also an effective cure.

The researchers are also working on coupling the same and slightly different techniques with immunotherapy. “Ultimately, we feel that this combination of ablation, drug and immunotherapy will be very powerful,” wrote Ferrara.