Tumours treated with chemotherapy drugs guided and measured by MR imaging

21 Feb 2011

Royal Philips Electronics and Eindhoven University of Technology have developed a method of MRI-guided chemotherapy delivery to tumours to improve treatment without increasing adverse side effects.

Image-guided drug delivery has been studied by scientists around the world for almost a decade because it may enable a beneficial increase in tumour 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 with their system an improved local drug uptake in tumours is achieved and that it can be visualized and measured in real time. These measurements may also give an indication at time of delivery if drug uptake in the tumour was sufficient, or if an additional treatment may be needed.

This proof of concept is published in the Journal of Controlled Release [1].

Cancer chemotherapy treatment is used to kill tumour 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 tumours, Philips and TU/e achieved an increased chemotherapy drug dose at the tumour site.

Some tumours contain sections poorly supplied with blood, which means that chemotherapy drugs are then not taken up evenly in the tumour. 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 tumour 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, tumours 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: 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.

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 tumour. The latter is mildly heated using a focused ultrasound beam causing the temperature-sensitive liposomes in the tumour to release their drug payload.

Simultaneous MR imaging is used to locate the tumour, 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 tumour 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.

“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.”


1. de Smet et al. Journal of Controlled Release 150 (1), 102-110 (2011).


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