Collaboration to Measure, Visualize Local MR Drug Delivery to Tumors

A joint research team has now demonstrated in preclinical studies that an improved magnetic resonance (MR)-guided drug delivery technique in which local drug uptake in tumors is achieved, can be visualized and measured in real time. These measurements may provide an indication at time of delivery if drug uptake in the tumor was sufficient, or if an additional treatment may be needed.

The research collaboration was initiated by Philips Medical Systems (Best, The Netherlands) and Eindhoven University of Technology (TU/e; The Netherlands). Image-guided drug delivery has been studied by scientists all around the world for almost a decade because it may enable a beneficial increase in tumor chemotherapy drug levels, thereby increasing treatment efficacy without an increase in adverse side effects. This proof of concept research was published in the Journal of Controlled Release in February 2011.

Cancer chemotherapy treatment is used to kill tumor cells and is more effective at higher doses. However, the applicable dosage levels are limited by potentially severe adverse effects to the rest of the body. In preclinical studies using their local drug delivery proof-of-concept system designed for the treatment of specific types of tumors, Philips and TU/e achieved an increased chemotherapy drug dose at the tumor site. Some tumors contain sections poorly supplied with blood, which means that chemotherapy drugs are then not taken up evenly in the tumor. As a result, some regions receive suboptimal doses and they are therefore not effectively treated with chemotherapy. Methods for visualizing and measuring drug uptake in the tumor at time of delivery were demonstrated in the preclinical investigations. Such information may give an indication directly after the treatment if drug uptake was sufficient. Based on this additional information, tumors that did not receive a sufficient drug dose due to their morphology may be candidates to receive an alternative therapy.

The research was performed under the leadership of Holger Grüll, a professor in the biomedical nuclear magnetic resonance (NMR) research group at the Eindhoven University of Technology and responsible for research into molecular imaging and therapy at Philips Research. Philips and TU/e have been working together in this exploratory research, which is also part of the EU-funded (Framework 7) European Research project Sonodrugs, for two years. The study was performed in a designated joint infrastructure in Eindhoven. Prof. Grüll and his team used a combination of MRI and ultrasound technologies together with temperature sensitive drug-carrying particles (liposomes) for local chemotherapy drug delivery.

The liposomes, injected into the bloodstream, transport the drug around the body and to the tumor. The latter is mildly heated using a focused ultrasound beam causing the temperature-sensitive liposomes in the tumor to release their drug payload. Simultaneous MR imaging is used to locate the tumor, measure local tissue temperature, and guide the ultrasound heating. To track the amount of drug released, the liposomes also contain a clinically used MRI contrast agent, which is co-released on heating. The release of the contrast agent can be monitored with MRI, allowing correlated measurements and visualizations of drug uptake in the tumor and surrounding tissue.

The preclinical studies demonstrated proof-of-concept feasibility of the local drug delivery method and the measurement and visualization of drug release. Additional preclinical studies are currently being performed to evaluate the therapeutic value of the technique, which is the next necessary step for clinical translation towards a therapeutic application in patients.

"Image-guided drug delivery technology has the potential to improve chemotherapy cancer treatment for certain types of cancer,” commented Henk van Houten, senior vice president and general manager at Philips Research and program manager healthcare. "Researchers from the Philips-TU/e collaboration are among the leaders in developing the MRI, ultrasound, and liposome combination technology for local drug delivery. Collaborating with partners and building on Philips' strength in medical imaging, we have shown that early feedback at the time of localized drug delivery treatment is possible, which could ultimately enable more informed treatment planning for better patient outcomes.”

Related Links:
Philips Medical Systems
Eindhoven University of Technology