A recent publication by Holger Grüll, Ph.D. and his colleagues has been hailed as an important development in the SonoDrugs project. Launched in November 2008, SonoDrugs is a multinational, 15-partner research consortium backed by the European Union’s Seventh Framework Programme (FP7) and aimed at holding the line on healthcare expenditures while providing access to state-of-the-art medical care. The consortium is developing new therapeutic options for cancer and cardiovascular disease that offer greater efficacy, reduced side effects, fewer burdens on the patient and faster recovery times than existing treatments.

SonoDrugs researchers are combining MR imaging, ultrasound and liposome technologies to develop delivery methods that release drugs locally at the diseased tissue site. These methods are designed to be triggered by focused ultrasound induced pressure or temperature stimuli.

The paper by Grüll and his colleagues, “Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: An in vivo proof-of-concept study,” was published in the February 2011 Journal of Controlled Release. Its key findings were:  1) local delivery improves drug uptake in tumors and 2) drug uptake can be visualized and measured by MR imaging in real time.

The preclinical research used temperature sensitive liposomes and a combination of MR imaging and ultrasound technologies for local delivery of chemotherapy. The liposomes contained doxorubicin and a clinically used contrast agent based on gadolinium. Because it could be tracked by MR imaging, the contrast agent enabled researchers to visualize and monitor drug uptake in the tumor and surrounding tissue in real time.

Real time capability is expected to be a significant advancement when this new method enters clinical use. It will enable physicians to determine if a tumor is absorbing sufficient chemotherapy or if additional or alternative treatment is needed. Insufficient drug absorption can occur in tumors with poor blood supply, which cannot be detected during existing cancer treatments.

Although encouraged by the findings, Grüll says, “I would like to be yet cautious about the translational value of our approach. We are dealing with a formulation that contains a gadolinium-based contrast agent and doxorubicin, so we have to first make sure about toxicity and toxicity profiles. Many things have to be sorted out and much more work has to be done in the preclinical space before we can bring this approach further in the direction of the clinic.”

He adds, “Preclinical studies are now determining if improved drug delivery enhances survival rates. I hope that within the next year we will have that data.”

Ultimately, Grüll believes that temperature induced drug delivery will become an important special application for cases that cannot be address with conventional approaches. “I think the technique has strong value for metastatic tumors that are localized and confined. For example, it may be a good option for pancreatic cancer or liver cancer patients who have a localized tumor that cannot be treated in any other way.”

Written by Ellen C., McKenna

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