Craig Malloy, M.D.
Craig Malloy, M.D., and his colleagues are using 13C-labeled chemicals in magnetic resonance spectroscopy (MRS) to measure the flux of metabolic pathways in the brain and heart. Since 13C is a stable isotope of carbon, it is safe for use around the lab and in patients. More importantly, 13C tracer studies provide much more information than classical radiotracers. Consequently a major focus is to develop methods to detect 13C and harness this information for clinical applications.
In their basic brain studies in animals, they are measuring fluxes through the neural metabolic pathways responsible for synthesizing neurotransmitters. These are the signaling molecules by which one neuron triggers its neighbor to launch a nerve impulse. Such in vivo MRS studies offer the potential for much greater basic understanding of the brain's neurotransmitter machinery, because previous studies have been restricted to analysis of the two basic types of brain cells—glial cells and neurons—grown separately in culture. However, these two cell types interact intimately in the living brain, meaning that in vivo studies enable a more realistic analysis of brain metabolism.
The researchers are also applying their MRS techniques to studying the neurotransmitter metabolism of the human brain. Such studies could reveal significant insights into neural function in the brains of both healthy people and those with such neurological disorders as Alzheimer's disease.
Dr. Malloy, Robert Bachoo, M.D., Ph.D., and their colleagues are also using 13C -labeled glucose as a tracer to analyze the metabolic pathways of brain tumors. One objective of these studies is to understand the role of high levels of lactate, a breakdown product of pyruvate, in brain tumors. While some researchers believe that lactate is a mere marker of brain tumors, others have developed evidence that it is a basic stimulant of the abnormal growth of tumors. Such insights could lead to improved treatment plans to battle such aggressive brain tumors as glioblastomas. In this research, they are using a mouse model in which human brain tumors are implanted in mice. This model, developed by Dr. Bachoo, constitutes a more realistic model of brain tumors, compared to cultured tumor tissue. While cultured cells alter their genetic characteristics, the implanted tumors maintain the same genetic profile as tumors in humans because they exist in a highly similar physiological environment. Neurosurgeon Bruce Mickey, M.D., and oncologist Elizabeth Maher, M.D., Ph.D., are working to translate these methods to in vivo measurements in the operating room to evaluate the actual metabolic pathways in human tumors in the brain.
To improve measurement of breast cancer response to chemotherapy, Dr. Malloy and colleagues at Texas A&M University are developing RF coils for the 7 Tesla MRI scanner that are tailored for detecting the breast cancer biomarker choline. The choline level in breast tumors is believed to be a good measure of malignancy because choline is a key component of the cell membrane. Thus, rapidly proliferating cancer cells will have high choline levels, given their need to build new cell membranes continually. Developing choline-specific RF coils will enable oncologists to use MRI to measure noninvasively a tumor's response to neoadjuvant chemotherapy given before surgery to shrink tumor size. If the tumor is responding, choline levels would drop, as the cancer's proliferation slows. Such a choline measurement could tell oncologists whether neoadjuvant therapy is working, also enabling patients to avoid chemotherapy if it is not proving effective.
For publication information please view Dr. Malloy's faculty profile.