Dean Sherry, Ph.D.
Dean Sherry, Ph.D., and his colleagues are developing 13C tracer molecules to be used with MRI to measure flux through metabolic pathways in cancers, the heart, and the liver. They are also developing molecules to enhance imaging of tumors using MRI. Such imaging offers unique potential for precise, non-invasive determination of cancer malignancy and response to therapy.
Dr. Sherry and his colleagues are exploring the use of hyperpolarized 13C pyruvate as a metabolic imaging marker for prostate cancer. They are also studying the use of hyperpolarized gluconolactone to follow flux specifically through the pentose phosphate pathway, which is believed to be particularly activated in cancers. Such measurements could offer a quantitative, non-invasive measure of tumor grade or malignancy.
The researchers are also developing hyperpolarized 13C benzaldehyde as a marker to measure aldehyde dehydrogenase activity in cancer cells. This effort is of particular importance because researchers believe that aldehyde dehydrogenase activity is characteristically high in cancer stem cells, which some research has indicated are central drivers of malignancy and metastasis in cancers. Thus, measuring such activity could offer fundamental insights into the role of stem cells in tumorigenesis, as well as possible targets for new cancer therapies.
Radioactive fluorodeoxyglucose (FDG) is widely used in positron emission tomography (PET) as a tracer to mark tumors. FDG mimics glucose, although it is not broken down in the cell. Since tumors use more glucose than normal tissues, they take up more FDG, and this higher concentration reveals tumors as "hot spots" in a PET scan. In their work, Dr. Sherry and his colleagues are designing a non-radioactive hyperpolarized counterpart to FDG that could be used similarly in MRI scans to reveal tumors. Not only would this glucose-mimicking molecule concentrate in cancer cells, it would be metabolized like normal glucose. So tracing this metabolic activity could give clinicians biochemical insights into a tumor, such as its malignancy.
Working with AIRC medical director Craig Malloy, M.D., Dr. Sherry is also developing MRI techniques and hyperpolarized 13C molecules that track the flux through metabolic pathways in the heart. In normal heart muscle, hyperpolarized 13C pyruvate is rapidly metabolized in the TCA cycle to bicarbonate. So, an MRI scan showing the distribution of hyperpolarized 13C bicarbonate could be used to map normal heart muscle, also revealing the presence of damaged tissue.
Dr. Sherry's laboratory is also developing contrast agents for molecular imaging of cancer. Such agents are chemicals that influence MRI relevant properties of water in tissues, to create higher contrast between the tissue and the surrounding water. In their work, Dr. Sherry and his colleagues are developing targeted paramagnetic chemical exchange transfer (PARACEST) agents for cancer imaging. These chemical complexes are engineered to attach selectively to molecules in tumors, and when magnetic pulses are applied, to influence the magnetic properties of water in the tissue, enhancing contrast in the tumor images. Such imaging could offer new diagnostic information about tumors and also enable assessment of the effectiveness of cancer therapies.
For publication information please view Dr. Sherry's faculty profile.