Molecular Imaging Scientific Themes
Theme 1. Synthesis and development of new methods to image tumor pathways and drug pharmacodynamics
This includes work on optical, Positron Emission Tomographic (PET), and MR techniques to measure tumor pathways, predict drug activity, and monitor treatment response. Innovative three-dimensional culture techniques have also been developed to explore tumor pathways using optical approaches and to test new drugs. Probes for a number of pathways have been developed including EGFR, PI3K, bcr-ABL/c-KIT, and histone deacetylases. Labeling of therapeutic agents, including small molecules, antibodies and nanoparticles are being done to track their clearance and tumor retention. In addition to imaging antibodies, other new approaches to imaging immunotherapy are being developed including α-methyl-L-tryptophan (AMT) to study immune resistance mediated by abnormal tryptophan metabolism via the kynurenine pathway. To assist in imaging the distribution of immune cells both AMT and FDG PET tracers are in use and new MR methods employing cells tagged with ferritin are under development. Additionally, new magnetic resonance and spectroscopic techniques, which better measure tumor blood flow and metabolism are being developed. These include methods to measure the acidic and oxidative states of the tumor environment while improving contrast. An important strength of the Program is the close collaboration among the imaging scientists, since imaging studies often now include more than one modality and seek to translate results from the lab to the clinic. Members with complementary expertise work with colleagues in other KCI Programs to apply our imaging skills to answer important biologic and clinical questions. Imaging is also being used to complement analysis of genomics and expression being done on biopsy and resected specimens. While genomic analyses can measure thousands of genes, imaging allows investigators to study tumor heterogeneity and non-invasively obtain repeated measurements over the course of tumor growth and treatment. Furthermore, functional measurements obtained with imaging can assist in demonstrating that a particular pathway is active and important in tumor physiology, something that simple measurements of gene expression may not be able to demonstrate.
Theme 1 Accomplishments
Theme 2. Imaging diagnostics for risk assessment, detection, radiation targeting and response to therapy
This theme involves imaging biomarkers that provide information to assess risk and detect cancer. It includes small and large-scale trials and methods to improve radiation treatment. It incorporates the development of new ultrasound methods such as tomographic imaging of the breast for use in the assessment of risk associated with breast density, as well as tumor detection and treatment response. These studies are being done in collaboration with investigators from Molecular Therapeutics and Population Studies & Disparities Research Programs to assess how such results are communicated to both patients and physicians and can be used to monitor and alter therapy. Image guidance has always played an important role in the delivery of radiation therapy, but it is even more critical in the use of the precise delivery of treatment possible with our new proton facility. A number of trials are now underway to optimize such treatment and studies are being done to better understand the radiobiology. The planned acquisition of a combined magnetic resonance/linear acceleration will also allow the study of variations in daily delivery of radiation and ways to improve targeting. Furthermore, pilot studies are already underway to use this MR/Linac to measure changes in tumor physiology over the course of treatment, such as apparent diffusion coefficient, vascularity and oxygenation, to help predict treatment failure and design methods to improve outcome. Members of the Program also work to use imaging as part of national trials under the NCTN and large registry trials. For example, 3'-fluoro-3'-deoxy-thymidine (FLT), which was developed at KCI, is being used to assess treatment sensitivity and response in breast cancer in local and NCTN trials, innovative therapy with lung cancer is being studied with KCI colleagues, and national trials in leukemia and melanoma are beginning. Nationally over 360,000 patients have been studied with PET using FDG and NaF with the direction of KCI investigators involved in National Oncology PET Registry (NOPR), leading to expanded experience and national payer approval to use PET in both clinical research and routine care. This demonstrates our commitment to take imaging technologies from the laboratory to widespread use in caring for patients.
Theme 2 Accomplishments