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PROJECT

Molecular Imaging of Disease Targets

Molecular Imaging of Disease Targets

Imaging is an essential non-invasive tool for building disease understanding and characterization. Contrast agents or targeted imaging (molecular imaging) allow specific features to be delineated, such as vascularization, abnormal metabolism, or disease-specific biomarkers. GE Research has an active program developing molecular imaging agents that benefits from our strong capabilities in diagnostic imaging hardware and histopathogical technology for characterization of biomarkers in diseased tissue.

Oxidative Stress (OS) is a fundamental pathogenic state in which reactive oxygen species exceed a cell’s antioxidant defenses, unless relieved cellular death will occur.  Understanding the OS state of tissue can provide valuable information on the presence of disease and/or assessment of therapeutic efficacy and potentially modification of the therapeutic intervention. GE Research has developed a 18F-FASu as a MI agent for OS. The vector (FASu) is a substrate for xCT, a transporter that imports cystine into cells.  Cystine is a substrate for the biosysnthesis of glutathione which is an important component of a cells anti-oxidant defense response; the expression of this transport system is upregulated by cells undergoing OS. The beacon is 18F which radioactively decays to generate positron which are recorded by Positron Emission Tomography (PET) instruments to generate an image. Tissues undergoing OS accumulate 18F-FASu and show up as hot spots in an image. Our team is particulary proud of our publication (Webster et al (2014) J Nucl Med 55:657), which received the Editors’ Choice Award for being on the "Three Best Basic Science Articles" in 2014.

We have also conducted extensive research into nerve imaging. Nerves are critical to the functioning of a host of tissues and a key challenge for surgeons is to avoid unnecessary resection of nerve tissue during surgical interventions. We have developed a fluorescent molecular imaging agent that binds to myelin basic protein, which coats myelinated nerves such as motor and sensory nerves in the periphery. The fluorescent signal from the agent allows surgeons to more readily identify nerves during surgery in order to avoid unintentional damage.

Project Impact

To fully realize the promise of precision medicine and targeted therapies, physicians need to have biological information about diseased tissue in order to select the best therapy and monitor therapeutic efficacy.  Indeed, “companion diagnostic” tests are required for some drugs in order to identify patients who are likely to benefit from a drug and to monitor response to therapy.  Often this information can be obtained by measurement of disease-relavent biomarkers in bodily fluids (in vitro diagnostics) or by detailed histopathological characterization of biopsies of disease tissue.

However, in many diseases, circulating diseases biomarkers are not available or cannot be discerned from background or the diseased tissue may not be amenable to resection or repeated resections to obtain tissue.  In these cases, molecular imaging may be able to provide the needed information to guide the management of a disease.

Acknowledgment/Disclaimer: Development of the MI agent for oxidative stress was supported by NIH grant R01EB014250 Development of the nerve labeling agent was supported by NIH grant R01EB011872
  • Our Expertise

    Capabilities utilized for Molecular Imaging of Disease Targets project

  • Biosciences

    Working from the molecular scale through human health and disease by building novel technology solutions for cell analysis and imaging applications

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Publications
  1. Webster, J.M., Morton, C.A., Johnson, B.F., Yang, H., Rishel, M.J., Lee, B.D., Miao, Q., Pabba, C., Yapp, D.T. and Schaffer, P. 2014. Functional imaging of oxidative stress with a novel PET imaging agent, 18F-5-fluoro-L-aminosuberic acid. Journal of nuclear medicine: Society of Nuclear Medicine, 55(4), p.657.
  2. Cotero, V.E., Kimm, S.Y., Siclovan, T.M., Zhang, R., Kim, E.M., Matsumoto, K., Gondo, T., Scardino, P.T., Yazdanfar, S., Laudone, V.P. and Tan-Hehir, C.A. 2015. Improved intraoperative visualization of nerves through a myelin-binding fluorophore and dual-mode laparoscopic imaging. PloS one, 10(6), p.e0130276.

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