Biomarkers research and development
Molecular targeting of specific receptors, transporters, enzyme s and other biomarkers are carried out by identifying and/or designing small molecules that can be radiolabeled with radioisotopes for PET or SPECT imaging. Cellular and molecular markers (biomarkers) that may be potential indicators of disease progression are sought out for developing imaging probes. A dysregulation of the biomarker or a loss in the biomarker or an increase in the levels of the biomarker may be detectable by an in vivo imaging probe and assist in diagnosis of disease as well as treatment planning. Once a molecular target and/or biomarker is identified, the process of small molecule design and synthesis is undertaken. This approach has been used successfully in our laboratories over the last two decades in optimizing imaging agents such as Fallypride and Desmethoxyfallypride for dopamine D2/D3 receptors, Mefway for serotonin 5HT1a receptors, Nifene for nicotinic receptors, all of which have now been taken to human studies.
Radiopharmaceuticals Production
Molecules to be radiolabeled are identified based on the binding and selectivity of the small molecule to the molecular targets and/or biomarker. Generally speaking, design of a suitable small molecule takes into consideration the ability to readily and rapidly radiolabel the molecule with radioisotopes such as carbon-11, fluorine-18, iodine-123. Automated radiosynthesis units are used to develop the radiolabeling methods, develop procedures of purification and quality control and assurance is validated as in 18F-fallypride and 11C-fallypride. A standard operating procedure (SOP) for the particular radiopharmaceutical is developed. Subsequently the radiopharmaceutical is taken to in vitro and in vivo preclinical testing.
Pharmacology and Neuroscience
Pharmacological testing involves measurement of binding affinities of the new compounds for the various targets sites, including receptors, transporters and other protein targets. Homogenate binding assays and autoradiographic methods using the Cyclone phosphor imager are used and data is analyzed using various programs such as Optiquant, KELL and Grafit. In vivo imaging, ex vivo imaging and autoradiographic studies are carried out to study neurotransmitter- receptor interactions like dopamine and drug interactions like clozapine. Studies are carried out with various labeled compounds (tritium, carbon-11, fluorine-18, iodine-123, iodine-124, gallium-68 and others).
Small animal PET Imaging
A state of the art Inveon Dedicated PET scanner from Siemens with a high-resolution of 1.4 mm is available for small animal studies. It can do whole body imaging of rodents, rabbits and other small animals. The facility is equipped to carry out detailed in vivo and ex vivo studies of various biomarkers.
Small animal CT Imaging
The facility is equipped with a state of the art Inveon Multimodality (MM) CT from Siemens, which has a resolution of up to 30 microns. The high resolution of the CT allows various applications for orthopedics, cardiology, oncology and others. The Inveon PET and CT are installed in tandem and can be used to carry out PET/CT imaging.
Large animal PET
Preclinical Imaging has unique opportunities for translational research. A high-resolution (4 to 4.5 mm) ECAT HR+ whole-body research scanner is available for human and large animal research. This equipment allows rapid transition from animal studies to human research studies. This facility if fully equipped to carry out various studies of neuroscience, oncology, diabetes, cardiology and others. In addition to the capabilities of preclinical imaging facility, translational research is enhanced by collaborations with various Centers and Departments at UCI. Multimodality imaging is an area of research which will be strengthened by ongoing work at other Centers at UCI.
Optical Imaging
In vivo fluorescence imaging is being used to optimize biomarkers for PET and assist in longitudinal studies. An in vivo Kodak imaging system F (Image Station 4000MM) is used for these studies. The system features 5-position excitation filter slider with two excitation filters of choice, 4-position emission filter wheel with two proprietary wide-angle emission filters of choice, external 150-watt halogen illumination source and mounted fiber-optic light guides, PC computer with 17-inch flat-panel monitor, KODAK Molecular Imaging Software. The CCD camera presents 4.2 megapixel resolution, true 16-bit imaging and high sensitivity.