Pilot Studies Program
CMGI has a limited amount of funding available to support pilot projects! These pilot funds are expected to be used to generate preliminary data for grant applications. Funding can be used for imaging or radiochemistry development projects and can be used to cover imaging time, radionuclide production, radiotracer synthesis, contrast agents and data analysis. Each grant will typically be in the $2,000 – $4,000 range, although applications up to a maximum of $10,000 will be considered, particularly for investigators developing new radiotracers. Further information and applications are available at Pilot Studies.
FREE Introductory Use of MicroXCT-200 Specimen Scanner
Investigators are invited to scan 2 specimens, which may include multiple scans of a single specimen, at no charge until January, 2013. Subsequent specimen scans will be recharged at the approved Specialty Equipment and Labor rates (http://imaging.bme.ucdavis.edu/faqs/recharge-rates/). The Labor rate will only be charged for the setup time, typically 0.5-1 hr. The MicroXCT is a high resolution scanning instrument that can achieve 1-5 mm resolution in samples a few centimeters in size. It may be used for both non-biological and ex-vivo biological specimens.
Announcing 3 New Imaging Instruments
The Center for Molecular and Genomic Imaging (CMGI), one of two facilities comprising the Shared Animal Imaging Resource, is receiving three new state-of-the-art imaging instruments funded with grants totaling more than $1.3M from the NIH Shared Instrument Grant Program (S10). These dedicated small-animal and small-specimen imaging instruments will add significant new capabilities to the Shared Animal Imaging Resource by extending the CMGI’s slate of preclinical imaging modalities, which currently include the in vivo imaging technologies PET, SPECT, MRI, CT, optical and ultrasound imaging.
First, a new IVIS Spectrum (Caliper/PerkinElmer) will replace an older model (IVIS 100; Xenogen) that was primarily used for bioluminescence imaging. The system will be installed in mid 2012. The Spectrum offers improved bioluminescence imaging and adds the capability for advanced fluorescence imaging.
CMGI will acquire a MicroXCT-200 (Xradia) in mid 2012. This system provides researchers with the ability to perform CT imaging of biological specimens with high image contrast down to a resolution of approximately 1-5 micrometers for ultra-high resolution imaging of specimens as large as a few cm.
Lastly, CMGI has just installed an Optical Imaging Cryomicrotome (Barlow Scientific) that is able to acquire high-resolution (10-30 um) fluorescence images of frozen tissue sections or rodent whole bodies. The microtome can cut sections down to 25 micrometers thick from specimens as large as 11cm x 24cm in size. A CCD video camera mounted with motorized excitation and emission filter wheels provides high-resolution fluorescence images for quantitative analysis of fluorescence distribution.
Copper-64 in Trial Production at CMGI
The radiochemistry/cyclotron facility at CMGI has completed a successful trial production of copper-64, in anticipation of routine production later this year.
Copper-64 (64Cu) is a positron emitting radioisotope with a half life of 12.7 hours, substantially longer than that of fluorine-18 (18F; 109 minutes) or carbon-11 (11C; 20 minutes), which are also produced at CMGI for positron emission tomography (PET) imaging studies. Longer lived radioisotopes are often better suited for radiolabeling PET targeting molecules that require many hours or days to reach optimum target-to-background ratios, such as antibodies and large molecules. 64Cu allows PET image acquisition for 1-2 days after injection.
Cyclotron production of 18F and 11C is routine and performed at PET centers worldwide. Cyclotron production of 64Cu is limited to a few research centers, which supply 64Cu for studies at UC Davis, and dozens of other sites nationwide. CMGI committed to 64Cu production to support the growing number of 64Cu projects at UC Davis, and to better protect them from disruptions in supply. Funding for the necessary equipment to upgrade CMGI facilities for 64Cu production came from an NIH shared instrumentation grant.
How 64Cu is produced
Cyclotrons produce radioisotopes by bombarding target atoms with a proton beam, converting them to the desired radioactive atoms. In the case of 64Cu, the target atom is nickel-64 (64Ni), a nonradioactive, but rare, isotope of nickel. To prepare 64Ni for bombardment, it is dissolved in acid, buffered, and electroplated to an inert metal disk. This disk, about the size of a quarter, is deposited into a target chamber and positioned for bombardment with a focused proton beam.
After bombardment, the irradiated disk is ejected from the chamber and transferred to a processing unit. There, the 64Ni/64Cu is dissolved in acid and stripped from the disk (only a small fraction of 64Ni has been converted to 64Cu, typical of all cyclotron productions). The 64Ni is separated from 64Cu by anion exchange chromatography, and reserved for reuse. The 64Cu is dried and redissolved in high concentration in a weak acid solution, now ready for the chemist to radiolabel PET targeting molecules.
Contaminant metals can lead to the production of unwanted isotopes, so high purity reagents and acid washed glassware are used during electroplating and processing to assure that no other metals are introduced to the process. 64Cu product is analyzed by gamma spectrometry, which can detect distinct energy signatures of contaminant isotopes, to assure its purity.
The first trial production of 64Cu at CMGI was performed in July 2011, and fully met the target specifications for quantity produced and radionuclidic purity. Several more trial productions will be performed to optimize production and processing, and assure reproducible quantity and purity. Routine, twice monthly production is planned before the end of 2011.
C-11 PET Tracers Now Available
First tracers in routine production bind to dopamine receptors
Raclopride and [11C]SCH23390 are being used in a UC Davis study of the neurological basis of social bonding of the Titi monkey. Above, a transaxial brain image after administration of [11C]raclopride shows selective uptake in the putamen. Image courtesy of Professor Karen L. Bales.
The CMGI Radiochemistry laboratory now produces [11C]SCH23390 and [11C]raclopride, two PET tracers for studying regional in vivo binding of ligands to dopamine receptors. These are the first 11C neuro tracers in routine production at CMGI.
Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. PET enables noninvasive direct measurement of components of the dopamine system in the living brain. Selective, high-affinity PET radioligands have been developed to study individual subtypes of dopamine receptors. [11C]SCH23390 and [11C]raclopride are tracers for the most extensively studied dopamine receptor subtypes, D1 and D2/D3, respectively.
To synthesize the PET tracers, 11C is produced on site with the Siemens RDS111 Biomedical cyclotron, and delivered to an automated gas-phase production (GPP) synthesis unit. GPP produces tracers of high specific activity; that is, the mass of tracer per imaging dose is exceptionally low.
Other well established tracers currently available at CMGI include [18F]FDG, [18F]FLT, [18F]FMISO, and [18F]FHBG. Method development is now underway for [11C]PK11195, which has been extensively used in studies of the peripheral benzodiazepine receptor.
As a service to investigators interested in a specific 11C or 18F tracer, CMGI can provide cost estimates for method development and tracer synthesis in support of grant applications. If you are interested in CMGI production of a specific PET tracer, please contact Doug Rowland at email@example.com.