Tumours treated with chemotherapy drugs guided and measured by MR
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 .
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
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
“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).