Published on: 07 February, 2011
Researchers at Eindhoven University of Technology and Philips Research have together developed a new technology for cancer treatment. The technology involves local administration of chemotherapy, with live monitoring by MRI of how well the medicine is taken up by the tumor.
The research was performed under the leadership of Holger Grüll, professor in the Biomedical NMR research group at the Eindhoven University of Technology and also responsible for research into molecular imaging and therapy at Philips Research. The proof of concept of this new technology will be published in Vol 150, issue 1 of the Journal of Controlled Release (February 2011).
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. The joint research team has now demonstrated in pre-clinical studies that an improved local drug uptake in tumors is achieved, and that it can be visualized and measured in real time. These measurements may give an indication at time of delivery if drug uptake in the tumor was sufficient, or if an additional treatment may be needed.
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 pre-clinical studies using their local drug delivery proof-of-concept system designed for the treatment of certain 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 sub-optimal doses and 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 pre-clinical 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.
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 work was performed in a designated joint infrastructure in Eindhoven. Grüll and his team used a combination of MRI and ultrasound technologies together with tiny temperature sensitive drug carrying particles (called 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. In order to monitor 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 pre-clinical studies from Grüll and his team described in the Journal of Controlled Release paper demonstrated proof-of-concept feasibility of the local drug delivery method and the measurement and visualization of drug release. Further pre-clinical studies are currently being performed to assess the therapeutic value of the technique, which is the next necessary step for clinical translation towards a therapeutic application in patients.