Facilities and equipment
We currently have a radiochemistry laboratory at the UCSD Center of Molecular Imaging that is used for translational research and a radiochemistry laboratory adjacent to the SAIR that will be used to produce F-18 compounds for the rodent PET imager.
The UCSD Center for Molecular Imaging that is located approximately 2.5 miles from the SAIR in the CC, houses a Siemens EXACT HR+ and a CTI RDS-111 cyclotron that is capable of generating F-18, N-13, and O-151. The facility has a 1,500 s.f. radiochemistry laboratory equipped with two hot cells, two mini hot cells, six automated radiochemical synthesis modules, two chemical fume hoods, one lead-lined fume hood, a MCA, a gas chromatograph, HPLC with multi-wavelength and radioactive flow-through detectors, an auto-well gamma counter, a radioactive stripscanner, a UV/visible spectrometer, two dose calibrators, a rotary evaporator with a high vacuum system, a high purity water system, and a laminar-flow sterile bench. An UltraSPARC computer system at the PET facility is networked with UCSD so that images and data can be transferred to other special processing or data analysis computers located at UCSD. Software tools have been developed in IDL6.0 to allow sophisticated region of interest analysis in DICOM, ECAT7x, and INTERFILE image formats in static and dynamic image acquisitions. Tools for tracer kinetic modeling using state-space equations have also been developed in IDL. The software has been developed to be platform independent and currently runs on both SUN and PC workstations.
The radiochemistry service is responsible for preparing a number of radiolabeled precursors for use by the ICMIC investigators. All 99mTc chelates will be based on the recent development of the bi-functional single amino acid chelate (SAAC) for technetium tricarbonyl. The F-18 precursor molecule will be based on an active ester of fluorobenzoic acid for labeling peptides and proteins. Bifunctional copper chelates will be based on the active ester of cross-bridged macrocycle, 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane and are an alternative to F-18 when a longer physical half-life is needed. Note that all necessary analytical equipment to validate the radiotracers according to the American Chemical Society is available.
The radiochemistry group led by Dr. David Vera will help match the tracer with the specific goals of the investigator, radiolabel the tracer and assess its stability and then validate the tracer in vivo. Should they desire to assess enzyme activity, they will devise a scheme to assess that effect.
Choice of Radionuclide
The common radionuclides for Single Photon Emission Computed Tomography (SPECT) are 99mTc (half-life = 6hr) and 123I (half-life = 13hr). The positron-emitting radionuclides (with their half-lives) used most frequently are 15O (2.07 min), 13N (10 min) and 18F (109.7 min). The actual specific activity for the most-used PET radionuclides, is on the order of 37-185 TBq/mmol (1000-5000 Ci/mmol) at the end of the cyclotron bombardment. Therefore, this adioactive probe is injected at tracer levels (~nmol injected). Non-traditional PET radionuclides, such as Cu-64, Br-76, Ga-68 and I-124 are available commercially. The general theme is to match the physical and biological half-life, with the required resolution differentiating SPECT from PET.
Choice of the Approach of Using a Radiotracer
To determine the interaction of the drug with a desired binding site, e.g. receptor or enzyme, we will radiolabel the potential drug in such a way as to not disturb the biochemical parameter to be measured and use a radioligand with the desired properties. Usually co-injection is used, but pre-or post-injection may be required depending on the relative pharmacokinetics to validate target binding by competition. Radiotracers can be used for indirect measure of neurotransmitters. For example, neurotransmitter concentration changes can be measured with a reversible receptor radioligand indirectly after administering the potential drug, whose putative mode of action is through neurotransmitter release.