Imaging of Brain Tumors

Mark Goodman is a chemist who is interested in PET and SPECT radiotracer development of agents for use in the study of the brain and cancer with an emphasis on the design and evaluation of cocaine analogs, diarylsulfides and heterocyclic compounds for in vivo study of the dopamine, serotonin, and norepinephrine reuptake sites in neurodegenerative disease, psychiatric and addictive disorders. More recently, he has begun mapping of intracranial tumors with Jeffrey Olson using alicyclic and branched chain amino acids for in vivo study of regional amino acid transport in primary and metastatic brain tumors. In addition to radiotracer development, other research interests include the development of automated devices to facilitate the use of new radiotracers in clinical medicine.

Xiaoping Hu is a biomedical physicist who focuses on cognitive neuroscience and biomedical imaging. Several of his projects are related to brain imaging: 1) investigate the utility of higher magnetic fields in MRI and spectroscopy and to determine its application in biomedical research and clinical medicine in humans with Hui Mao. 2) develop a technique for the monitoring and compensation of physiology related fluctuation in image intensity of functional MRI. 3) investigate the utility and develop methods for mapping brain function in humans at 7 Tesla. 4) investigate the neural correlates of reading in normal and low vision.

Hui Mao is a chemist who is particularly interested in brain imaging and tumor diagnosis. Three of his research focuses are related to the brain tumor program: 1) develop clinical applications of in vivo and in vitro MR imaging and spectroscopy in cancer, particularly tissue characterization and metabolic assessment of the tumor; 2) Develop target specific MRI contrast agents for cellular and molecular imaging and their applications in detection and tracking cancer cells with Hyunsuk Shim; 3) Functional and metabolite mapping for pre-surgical planning using fMRI and MRSI with Jeffrey Olson and D.Brat.

Hyunsuk Shim is a biophysicist interested in improving molecular imaging for cancer. This involves (1) evaluation of CXCR4 antagonists as potential drugs for the inhibition of breast cancer metastasis and brain tumor growth. By labeling the antagonists with F18 and using PET for imaging she can determine the CXCR4 levels in primary tumors without biopsy, examine whether these levels correlate with metastatic potential and also establish the in vivo pharmacokinetics and localization of the antagonists. (2) non-invasive detection of Her2/Neu positive micrometastasis by F18-labeling of Herceptin (humanized anti-HER2 antibody) with Mark Goodman. By combining the high expression level of HER2 in breast cancer patients and superior sensitivity of F18-PET, it may be possible to detect single HER2-positive cells in any part of the body. (3) three dimensional magnetic resonance spectroscopic imaging (3D-CSI) of tumor metabolic markers (lactate and lipid) for mitochondrial dysfuction during chemotherapy. In addition, the effectiveness and the safety of the drugs can be monitored by lactate and N-acetylaspartate by using 3D-CSI with Hui Mao and X. Fu.

Jeffrey Olson is a neurosurgeon with a primary focus in clinical brain tumor research. This revolves mainly around Phase I and Phase II protocols developed within the NABTT CNS consortium exploring chemotherapeutic, biologic, radiation and surgical strategies. Specific interests include: 1) development of local delivery methods of radiation such as the Gliasite RTS, local delivery of chemotherapy such as the Gliasite Spectrum. 2) the use of novel antitumor agents such as PS-341. He maintains an interest in animal brain tumor modeling and collaborates with investigators at Emory, the University of Georgia and in industry to assess treatment toxicity and efficacy in intracranial models of brain tumor. 3) therapy choice based on specific tumor characteristics. Ultimately, it will be possible to determine if a specific tumor is a potential target for a given therapy based on its genetic or protein expression profile. To that end he continues to work on interferon alpha as a therapeutic agent. 4) metabolic imaging of brain tumors which offers the opportunity to evaluate therapeutic response before it is detectable by other imaging modalities. To this end he has a long established study with Mark Goodman in PET imaging and accrual of patients to these studies remain ongoing. In his clinical work he is assisted by Ian Crocker, a clinical radiation-oncologist, David Lawson, a medical oncologist and Nicolas Krawiecki, a clinical neurologist with an academic interest in the detection of endocrine disorders in children treated for brain tumors.

Nelson Oyesiku, along with Ian Crocker, is co-director of the stereotactic radiosurgery program, which provides radiosurgical treatment for patients with brain tumors. He is developing in vivo tumor imaging for clinically non functioning adenomas based on folate receptor overexpression. In collaboration with Endocyte Inc and Dr Low (Purdue University), he is using Technetium Tc 99m EC20 ,a radio-pharmaceutical that is an in vivo diagnostic for identifying folate-receptor positive tumors. This study is a screening Phase 2 study to evaluate the safety and efficacy of FolateScan (Technetium Tc 99m EC20) in patients with pituitary tumors. Ultimately, Folatescan could provide a non-surgical means of selecting folate receptor-positive pituitary patients that may benefit from folate-targeted therapy.