Berkeley researchers explore novel technique for hyperpolarized MR

Hyperpolarized atoms may pave MR's way into molecular imaging, but this future is in a much different direction than researchers have traveled so far.

Until recently, hyperpolarized gases, composed of optically pumped helium or xenon, have served as contrast agents that patients breathe in. The primary application of the gases has been to view the lungs, an area of the body from which MR is otherwise excluded. Research in the late 1990s with hyperpolarized helium and xenon addressed the potential of MR as a diagnostic tool for pulmonary disease. This area of study was attractive because of the dozen or so drugs that were then under development for chronic obstructive disease. But practical and economic challenges, along with regulatory changes and difficulties encountered in the development of these drugs, conspired to sink hyperpolarized MR.

Now researchers at the U.S. Department of Energy's Lawrence Berkeley National Laboratory and the University of California at Berkeley have come up with an experimental technique called Hyper-CEST (hyperpolarized chemical exchange saturation transfer) that they say could become a valuable tool for the diagnosis of diseases beyond the lung, including cancer.

In a paper published in the Oct. 20, 2006, issue of Science, the team concludes that this technique is about 10,000 times more sensitive than other molecular MRI techniques, describing it as a critical step toward the application of xenon biosensors as selective contrast agents in biomedical applications.

Xenon atoms, hyperpolarized with laser light, might be linked to specific proteins or ligands, said Alexander Pines, a professor of chemistry at UC Berkeley. Such links could create biosensors that eventually could generate highly selective images of cellular or even molecular targets.

"Hyper-CEST creates a strong signal in regions where the biosensor is present, allowing for easy noninvasive determination of the target molecule," Pines said. "This approach should be broadly applicable, potentially overcoming many shortcomings of currently used strategies for molecular imaging."

Hyper-CEST would be extremely sensitive as a diagnostic tool for cancer, because it could detect the presence of cancer-related proteins at micromolar (parts per million) concentrations, he said. Boosting the power of this technique is the ability to tailor the xenon biosensors to detect different proteins at the same time in a single sample.

"With Hyper-CEST, we could perform multiple virtual biopsies on a single tissue sample, using different biosensors to screen for each potential form of cancer," said Leif Schröder, a physicist at the Berkeley lab.

Creating such contrast agents, however, may not be easy. Optically pumped xenon atoms must first be caged in a molecular structure called a cryptophane. Biochemical tags must then be attached to the cryptophane to draw the assembled bioprobe to the target.

Although encouraging, much of the medical potential behind Hyper-CEST remains unproven. The Berkeley researchers thus far have tested Hyper-CEST only on a laboratory phantom. Their next step is to work with biological cells in culture, using antibody-targeted probes. Only then can they begin to seriously examine the possibilities that their technique may have as a medical diagnostic tool.