October 2009

CANCER:

Ultrasound Facilitates Molecular-Based Cancer Diagnosis

Confirming cancer and many other diseases often involves detecting the presence of a "biomarker" (a protein or some other molecule) in blood. A common challenge is that the biomarker may be present in low concentrations (difficult to detect), at least during the initial stages of the disease.

The initial stages of the disease are often the most treatable stages. Consequently, there are many technical protocols out there for detecting low concentrations of biomarkers in blood, each tailored to a specific disease.

However, as mentioned, there are one or more protocols available for each disease, and no universal method for detecting biomarkers. Additionally, the simple detection of biomarkers in blood may give no information on where it was produced, information which would help identify the cause and location of the condition one is trying to treat.

Sanjiv Gambhir, Gary Glazer (Stanford University, California) and coworkers have simplified this detection dillema, at least for detecting certain cancers. They have used low-frequency sound waves to detect colon cancer in mice.

Detecting cancer.

The general idea was to apply low-frequency sound waves to tumor cells, which induces the cells to release enhanced levels of the biomarker. You can envision this as shaking a bottle of mustard to get the flow going.

The scientists optimized the experimental protocol to avoid cell death. This involved tuning the frequency and power to low enough levels, and the time to short enough durations, in a way that still obtained the desired results.

In this case, the scientists were attempting to detect colon cancer. Their chosen biomarker was carcinoembryonic acid, which is routinely utilized as a colon cancer biomarker.

Experiments were performed in cells and in mice. They found that biomarker release could be enhanced from mice tumors using 6 minutes of ultrasound at a power of 2 watts per square centimeter.

A release of 0.36 nanograms of biomarker per milliliter of blood was observed. No statistically significant detectable amount of biomarker was released from tumors not subjected to ultrasound.

Additionally, one can envision performing these experiments all over the body, determining at which locations in the body ultrasound induced biomarker release. Thus, information on the location of the tumor is provided.

Future directions.

The scientists realize that their studies may not be generally applicable for detecting various cancers, both those which are visually observable and those that are still in the microscopic stage. Furthermore, cancer cells which inherently possess a very small amount of biomarker may not be detectable by this technique.

They also note that cancer cells underneath the surface of a bone will not be perturbed by low-frequency sound waves. However, the technique they have developed shows much initial promise, and should be pursued as a possible method to detect cancer while simultaneously figuring out the location of the cancer in the body.

for more information:
D'Souza, A. L., Tseng, J. R., Pauly, K. B., Guccione, S., Rosenberg, J., Gambhir, S. S., & Glazer, G. M. (2009). From the Cover: A strategy for blood biomarker amplification and localization using ultrasound Proceedings of the National Academy of Sciences, 106 (40), 17152-17157 DOI: 10.1073/pnas.0903437106