New PET Imaging Tracer Makes Tumors Visible in High Resolution

An international team of scientists has developed a new compound that enables specific tumor types to be rendered visible in high resolution using positron emission tomography (PET) imaging.

The tracer has effectively been evaluated in laboratory mice. The researchers are now planning clinical trials in humans.

Imaging techniques used for cancer detection and tracking provide a lot more than only data on the scale and location of cancerous ulcers. There are advanced techniques that additionally characterize the tumor cells precisely, for instance, by specific molecules they carry on their surface. Such additional information provides clinicians with vital clues as to the exact sort of cancer and enables them to predict the probability that a patient will respond to a particular form of therapy.

Researchers from ETH Zurich (Switzerland), the Paul Scherrer Institute (PSI; Villigen PSI, Switzerland), and Merck Millipore (Billerica, MA, USA) have now developed a new tracer for PET that binds to the folic acid receptor. This receptor is significant because it accumulates on the cell surface in many cancer types. The PET scan provides data on the size and location of the tumor and the density of the folic acid receptors on the cell surface.

The researchers, headed by Drs. Simon Ametamey and Roger Schibli, both professors at the Institute of Pharmaceutical Sciences at ETH Zurich, have successfully assessed their new substance in mice with cervical tumors. In a next phase, the scientists now want to study whether the substance proves equally successful in humans. A pilot study on patients with ovarian, lung and intestinal cancer in several Swiss hospitals, including University Hospital Zurich, is in preparation. It will be the first clinical trial on a folic acid receptor marker for PET on patients.

If the substance proves suitable, the scientists would like to use it to predict the effectiveness of chemotherapy in the future. They, most importantly, have a new generation of cancer medication in mind that also binds to the folic acid receptor, which then channels the drug into the cancer cells, where it unfolds its therapeutic effect.

“Our PET tracer provides important additional information for this targeted therapeutic approach with cytotoxic substances,” stated Dr. Ametamey. One difficulty with the new form of therapy is that not in all patients the cancer cells carry the folic acid receptor. In the instance of cervical, ovarian, and brain tumors, it is nine out of 10 patients, with lung cancer 75% and with breast cancer about 50%. In patients without the receptor, the novel chemotherapy is ineffective.

With the aid of the new technique, it could be possible to predict whether a patient will respond to such treatment. Patients whose tumors do not have any folic acid receptors could avoid this therapy and its side effects. Moreover, physicians can use the new PET tracer to optimize monitoring the progress of the therapy and study whether the tumor is shrinking.

However, the new PET tracer is not just interesting for cancer medicine, but also suitable for displaying inflammatory responses in the body. The folic acid receptor occurs also at the surface of specific cells of the immune system, the macrophages, and only if these are in a so-called activated state during an inflammatory response. The new marker substance could therefore be used to display inflammatory diseases such as arthritis, arteriosclerosis, or inflammatory bowel diseases with PET.

Moreover, a third arena of application is also imaginable for the substance: medication development. “If we’ve got a method to detect chronic inflammatory responses in a noninvasive way, we can test the efficacy of anti-inflammatory medication more effectively,” explained Dr. Schibli.

The study’s findings were published February 10, 2013, in the journal Bioconjugate Chemistry.

Related Links:
ETH Zurich
Paul Scherrer Institute
Merck Millipore