Researchers at Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH) have collaborated to develop a new magnetic resonance imaging (MRI) technique to identify which nanotherapeutics are the most useful for treating tumors in different patients. This technique has received the approval of the FDA.
MRI image (left) of a tumor shows nanoparticle accumulation in color. At the cellular level, tumor cells (blue), ferumoxytol (green) and a therapeutic nanomedicine (magenta) can be seen.
Currently a large ammount of research and clinical trials are being conducted on several nanotherapeutics, with many of these nanotherapeutics receiving clinical approval for the treatment of cancers. However, a method which predicts which treatment would be best for specific individuals has not been available.
Just as genetics is used in some cases to predict an individual’s response to a drug, we wanted to develop a companion diagnostic that can predict response based on physiological differences. We hypothesized that ferumoxytol – a product that has been approved for the treatment of anemia – could be used to identify tumors that are more likely to respond to a nanomedicine.
Miles Mille - MGH
Our goal is to develop new nanotherapeutics that can be safely and effectively delivered to cancer patients. One of the key translational challenges has been to better match patients to new nanotherapeutics based on patients’ physiology. Our work takes a precision medicine approach to nanotherapeutics: using this technique, we can predict how well drug-loaded nanoparticles will accumulate in a particular tumor.
Omid Farokhzad - BWH
The researchers considered that a patient’s unique physiology could determine how nanoparticles accumulate at different tumor locations. Certain patients could have tumors with specific physiological conditions which could enable nanoparticles to accumulate at a faster rate within tumors.
This accumulation phenomenon is considered to be due to an enhanced permeability and retention (EPR) effect. In mouse models of solid tumor cancers, the researchers tested ferumoxytol which is magnetic, allowing it to be imaged by MRI.
The investigators also used a fluorescent dye to label magnetic nanoparticles, which enabled them to microscopically view particle accumulation on a single-cell level. Each of the tumors was EPR categorized as either low, medium and high EPR. Following this, the investigators delivered a chemotherapeutic drug via nanoparticles to each tumor. More drug was delivered to tumors that had a higher EPR.
The MR imaging strategy developed by the team was able to accurately predict the amount of drug that would reach specific tumors, and hence, predict the response of the tumors to nanoparticles loaded with drugs.
This work represents a major stepping stone toward translating new discoveries of nanotherapeutics into clinical impact and selecting patients for nanotherapeutic trials.
Omid Farokhzad - BWH
The researchers now plan to conduct the studies in patients for clinical validation. Additionally, the types of cancer that would effectively respond to nanotherapeutics could also be determined with studies on different cancer types.
The research has been published in the journal 'Science Translational Medicine'.