Western alumnus and current postdoctoral fellow Todd Stevens, along with a research team at the Lawrence Berkeley National Laboratory (Berkeley Lab), have proposed a method of detecting lung cancer tumors at an earlier stage of development. Stevens, PhD’08 (Medical Biophysics), is a research associate with the Imaging Research Group at Robarts Research Institute.
The research team showed tiny bubbles carrying hyperpolarized xenon gas hold big promise for NMR (nuclear magnetic resonance) and its sister technology, MRI (magnetic resonance imaging), as these xenon carriers can be used to detect the presence and spatial distribution of specific molecules with far greater sensitivity than conventional NMR/MRI. Applications include molecular imaging of complex solid or liquid chemical and environmental samples, as well as biological samples, including the detection and characterization of lung cancer tumors at an earlier stage of development than current detection methodologies.
“Rather than the protons used as the reporting medium in conventional NMR/MRI, our reporting medium is the NMR/MRI-active isotope of xenon (Xe-129),” said chemist Alex Pines, who led this research along with Stevens and Matthew Ramirez.
Xenon is an ideal reporter because it is inert and nontoxic, and has no background in natural samples. It can also be hyperpolarized using established optical techniques, which facilitates detection of xenon NMR contrast agents at sub-picomolar concentrations. This is orders of magnitude below the threshold for detecting proton contrast agents in a conventional NMR/MRI system.
NMR and MRI are well-established technologies based on an intrinsic quantum property of atomic nuclei called ‘spin.’ While non-invasive and capable of providing information in a wide range of applications, NMR/MRI techniques have long been plagued by a lack of sensitivity.
In this latest development, Pines, Stevens and Ramirez combined a strategy called hyperCEST (for hyperpolarized xenon chemical exchange saturation transfer) with nanoemulsions that can be made to bind to molecular targets of interest. These emulsions consist of a perfluorocarbon core and a stabilizing surfactant that form droplets in water measuring between 160 and 310 nanometers in diameter.
The use of hyperpolarized xenon and perfluorocarbon nanoemulsions should prove especially useful for chemical sensing applications in which sparse analytes need to be detected from opaque mixtures that cannot easily be probed with optical-based techniques. Such mixtures include biofuels and other complex fluids, and the surfaces of nano materials and other novel solids. However, from the public’s perspective, perhaps the most intriguing potential application is the early diagnosis of lung cancer.
“Currently, the most widely used technologies for lung cancer diagnostics are X-ray CT and nuclear medicine techniques, all of which use ionizing radiation that precludes frequent screening and longitudinal studies,” Stevens said. “Our xenon-based MRI can probe the void space of the lung and the lung tissue directly and via chemical exchange. In addition to earlier detection of cancerous tumors, our technique also has the potential to allow for characterization of the types of cancer cells present.”
By using a library of targeting molecules on the outside of the nanoemulsion droplets, one could determine what agents are binding and infer information about the cancer cells based on the bound-targeting molecules.
“The next steps in this effort,” Stevens continued, “will be to extend control over the size and stability of the nanoemulsion droplets, which will enhance the contrast and distribution of the agents, and to optimize droplet targeting systems for some select applications.”
Following his PhD at Western, Stevens was an NSERC-postdoc with the Berkeley Lab and University of California-Berkeley from 2008-10. Located on the campus of the University of California-Berkeley, the Berkeley Lab is a U.S. Department of Energy national laboratory conducting unclassified scientific research. Stevens remained at Berkeley Lab as a physicist postdoc to extend his stay until March 2011. This research represents the last of his Berkeley work to be published.
The paper describing this research, Nanoemulsion Contrast Agents with Sub-picomolar Sensitivity for Xenon NMR, was published in the June 2013 edition of the Journal of the American Chemical Society.
