Research in Experimental Diagnostic Imaging
Research Laboratories in Experimental Diagnostic Imaging
The Department of Experimental Diagnostic Imaging (EDI) consists of several laboratories organized into different sections, which reflect a truly multidisciplinary nature of research in Molecular and Genetic Imaging of Cancer (MAGIC) that is being developed under the direction of professor and chairman, Dr. Juri Gelovani. The work in individual laboratories includes individual investigator/principle investigator-initiated research, as well as core-like research functions and materials development for intradepartmental (within EDI) and interdepartmental multidisciplinary basic, pre-clinical and clinical-translational collaborative projects at MD Anderson Cancer Center.
Experimental Diagnostic Imaging consists of several different core labs including chemistry, radiochemistry, genetics, molecular biology, animal models, transgenic animal models, molecular imaging and molecular imaging which includes different imaging modalities such as PET, SPECT, CT and MRI.
A variety of projects in imaging in cancer biology for diagnosis and molecular therapy of cancer using small molecular, micromolecular, nano-particle based, gene therapy based, adoptive cell therapy based and radiation-based therapy of cancer within these projects can be conducted in the laboratories emphasizing a variety of disciplines including but not limited to chemistry, radiochemistry, biology, bioengineering and medical physics.
The research and development (R & D) processes at different core and PI laboratories are highly integrated, because each laboratory conducts research, provides expertise and develops intermediate or final materials and methods within a particular segment of the R & D pipeline of novel molecular and cellular imaging agents and methods. Thus, materials and methods developed in one laboratory (or core) are moved to the next laboratory in the R & D pipeline. Such a structure of a department (indicative of an industrial company conveyer belt) minimizes the duplication (or multiplication) of resources and allows to harness the diverse spectrum of expertise of different faculty and facilities leaders, each of whom is dedicated to the development and clinical translation of novel tumor-targeted molecular-genetic and cellular imaging and imageable therapeutic ("theragnostic") agents.
Cyclotron and Radiochemistry Laboratories
These laboratories are essential for radionuclide production and radiolabeling of novel tracer molecules. Organic synthesis, radiochemistry and analytical chemistry facilities are being developed. A part of these laboratories is designed in compliance with the GMP certification requirements for clinical use of newly produced radiotracers.
Synthetic and Analytical Laboratories
These laboratories are crucial for synthesis, purification and characterization of various novel biologically active molecules that would be developed into new optical, PET and MRI/MRSI imaging probes, as well as synthesis of precursor molecules for radiolabeling, paramagnetic and fluorescent labeling. Dedicated synthetic chemistry and analytical equipment has been installed at this facility, which will complement and widen the spectrum of already existing analytical equipment at MD Anderson and Gulf Coast Consortium in Chemistry and Structural Biochemistry.
In silico Engineering and Modeling
This laboratory designs new molecules and screens ultra-large libraries (>100,000 compounds) using powerful computers and software. This technology is becoming more widely used in development of novel "designer" molecules and "smart imaging probes," virtual screening of large chemical libraries, for identification of lead compounds and for further optimization of these lead compounds in a rational and more predictable way.
High Throughput Screening
This laboratory will further develop methods of rapid assessment and characterization of large libraries of novel radiochemical compounds as potential lead candidate molecules for development into probes for non-invasive imaging. Currently, there are no high throughput platforms that could be routinely used for discovery and optimization of imaging agents, specifically; the majority of existing HTS platforms are developed for discovering various drug-like inhibitors, not molecular mimetics which meet the most important criteria of a tracer molecule – not to influence, but reflect the process.
Molecular Biology in Imaging
Laboratories in this section facility and subsidiary laboratories are required for the assessment of interaction of novel imaging tracer molecules with corresponding molecular and genetic targets, and for high throughput screening of novel lead compounds and radiotracers. Integration of these laboratories into the process of new imaging agent discovery is crucial to the success of the overall program.
This laboratory is essential for the assessment of imaging tracer interactions with the corresponding target protein (e.g., enzyme kinetics/inhibition), tracer metabolism in blood and tissues (sensitivity, specificity, etc).
Genetic Tracers Laboratory
This laboratory will develop novel imaging and therapeutic gene delivery vectors for non-invasive imaging in animals and in clinical patients. Genetic tracers will greatly facilitate the development and clinical implementation of novel gene therapeutic approaches by providing means for non-invasive whole body visualization and monitoring of the location, magnitude and duration of therapeutic gene expression over time.
Cellular Tracers Laboratory
This laboratory will develop novel "cellular tracers" including various types of immune-competent cells (T-cells, NK cells, stem cells, etc.) genetically labeled with different PET, MRI, fluorescence and bioluminescence reporter genes. The cellular tracers laboratory will be utilizing many of the vectors that will be developed by the genetic tracers laboratory. These cellular tracers will allow for the assessment of trafficking, targeting, activation, differentiation and long-term fate of therapeutic cells to kill cancer.
Animal Tumor Models and Therapy Laboratory
This laboratory (including transgenic and knockout models) will develop and produce clinically relevant animal models of various cancers for testing new imaging and therapeutic approaches in which the efficacy of imaging of a given therapeutic strategy will be evaluated.
MRI/NMR Spectroscopy and Imaging
These laboratories will develop and validate novel molecules and NMR spectroscopic/imaging methods to improve the detection/characterization of cancer cells and to study the metabolism of novel anti-cancer drugs. These laboratories will use a 9.4T research magnet for pre-clinical research that will be translated to the clinic using the 7T whole body clinical MRI/MRS system (GE Medical) once it becomes available.
Advanced PET Instrument Development
These laboratories developed a high-resolution PET system with close to 2 mm in plane resolution. Several novel PET systems are currently being developed, including the high-resolution variable aperture whole-body/breast (or head) PET system, the ultra-high high-resolution PET/CT system and the "micro-PET" system for animal imaging. This section has its own machine shop, circuit board printing and assembly facility, detector and electronics manufacturing plant, software development, instrument testing, etc. One of the high-resolution PET systems developed by this section will be used in-patient imaging for translational research.
Dedicated Animal Radionuclide, CT, Optical and NMR Spectroscopy Imaging and Small Animal Cancer Research Imaging Facility
The existing SACRIF imaging instruments are being and will be used to perform routine and established imaging studies to cover the immediate daily needs of different investigators at MD Anderson and industrial contractual studies (e.g., detection of tumor location and size, contrast agent-based imaging of blood flow/blood volume/permeability to detect and characterize tumors, micro-PET imaging with commercially available 18F-FDG, etc.). However, to sustain the high-volume of studies conducted and future planned by the researchers within EDI, a dedicated set of imaging equipment is required including: Micro PET, Micro CT, Micro SPECT/CT and a 9.4T (or HT) NMR Spectroscopy and Imaging.