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Nuclear Medicine: Research Resources

Nuclear Medicine Research Laboratory space comprises 21,000-sq. ft. of space located in two adjacent buildings, the Kresge Medical Research Buildings and Medical Sciences Building I. The laboratories include two cyclotrons and support including shop and stockroom (2,920 sq. ft.), PET radiochemistry (2,000 sq. ft.), PET organic chemistry (1,260 sq. ft.), PET animal imaging and support (704 sq. ft.), PET activation studies (170 sq. ft.), Image processing, programming, main computers (650 sq. ft.), biodistribution labs. (1,500 sq.ft.), PET/SPECT radiopharmaceutical chemistry (1,433 sq. ft.), Tumor Immunology (3,093 sq.ft.), Physics and Instrumentation Labs for PET/SPECT (1,243 sq.ft.).  Key features of these laboratories are described in the following sections.

Kresge Cyclotron/PET Facility
The Kresge Cyclotron/PET Facility is administratively within The Division of Nuclear Medicine, Department of Radiology, and has been operational since March of 1983.  The cyclotron/target systems, the radiochemical/radiopharmaceutical lab and the animal research PET tomographs with associated computers for data reduction and image processing comprise the major facility laboratories.

Radionuclide Production:  The Cyclotron Corporation (TCC) CS-30 accelerator is a four particle, fixed energy, positive ion, isochronous cyclotron, protons, deuterons, helium-3(++), and helium-4(++) ions are produced and are accelerated to energy of 26 meV, 15 MeV, 38 MeV, and 30 MeV respectively.  Maximum measured external currents are 60, 100, 60, and 40 microamperes respectively.  Typical operational beam currents on external targets are 10-40 microamperes.

The cyclotron is equipped with three external beam lines for target irradiations.  The middle beam line is fitted with a vertical target switching ladder containing eight separate targets.  Targets for the production of carbon-11 (as CO2 and HCN), nitrogen-13 (as ammonia or nitrates/nitrites), oxygen-15 (as O2, from either proton or deuteron reactions) and fluorine-18 (as fluoride ion) are currently in routine operation. 

The laboratory maintains complete radio-HPLC, radio-GC and radio-TLC systems to test chemical, radiochemical, and nuclide purities as well as for development of new positron emitting short-lived radiopharmaceutical agents.

Medical Sciences I Cyclotron and Radiochemistry Facility
In March 2005, The University of Michigan opened a new facility for production of PET radiotracers.  Comprising 5,000 net sq ft of new construction, the facility houses a General Electric PETtrace cyclotron, two radiochemistry laboratories with a total of 10 new Comecer hot cells and supporting chemistry and analytical laboratories for production of radiopharmaceuticals for human and animal studies. 

Radionuclide Production
The GE PETtrace is a two particle, fixed energy negative ion cyclotron.  It produces protons and deuterons and is capable of simultaneous irradiation of two targets (six targets are on the machine).   Targets for the production of carbon-11 (as C02 and HCN), nitrogen-13 (as ammonia or nitrates/nitrites), oxygen-15 (as 02, from either proton or deuteron reactions) and fluorine-18 (as fluoride ion) are currently in routine operation. 

The laboratory maintains complete radio-HPLC, radio-GC and radio-TLC systems to test chemical, radiochemical, and nuclide purities as well as for development of new positron emitting short-lived radiopharmaceutical agents.

PET Chemistry
A full spectrum of synthetic precursors – [11C]carbon dioxide, [11C]carbon monoxide, [11C]cyanide, [11C]methyl iodide, [11C]methyl triflate, [18F]fluoride ion, [15O]oxygen, [13N]ammonia - are readily available for both research and clinical radiopharmaceutical synthesis and are in clinical use. These include radiopharmaceuticals for blood flow ([15O]water,  [13N]ammonia), and metabolism ([18F]fluorodeoxyglucose, [11C]methionine, [11C]acetate, [11C]choline and [18F]fluorothymidine).  Aspects of neurochemistry in the heart and brain, including receptors, transporters and enzymes, are under study using a variety of radiopharmaceuticals ([11C]flumazenil, [11C]dihydrotetrabenazine, [11C]epinephrine, [11C]hydroxyephedrine, [11C]phenylephrine, [11C]N-methylpiperidinyl propionate, [11C]carfentanil, [11C]raclopride, [11C]methylphenidate, [11C]DASB and [11C]PIB).  Laboratory space for the PET Chemistry effort currently consists of radiochemistry laboratories (1,600-sq. ft.) and synthetic organic chemistry laboratories (1,260-sq. ft.).

Positron Tomographs for Animal Imaging
Both a microPET R4 tomograph and a microPET P4 from Concorde Microsystems, Inc. are housed within our research laboratories for animal studies.  The R4 system is for rodent (small animal) imaging, while the P4 has a larger field-of-view (FOV) sufficient for primate and small dog imaging as well as rodents.  Each system consists of 32 rings of LSO detector crystals providing an ~8 cm axial FOV.  The R4 scanner has 192 detectors per ring giving an in-plane FOV of ~10 cm, while the P4 scanner has 336 detectors per ring giving an in-plane FOV of ~21 cm.  Resolution for both systems is 2 mm.  Each tomograph is operated on a Dell Xeon dual 3.0 GHz processor workstation.  Additional PC systems are also available for image reconstructions and analyses.  Automated systems for assay of arterial blood radionuclide concentrations are readily available for efficient recording of sample times, well counter count rates, and automatic decay correction of the data.  Animal research on this system is used for the evaluation of new radiotracers developed in the nuclear medicine research laboratories, validation of new quantitative PET methodologies, as well as study of physiology and biochemistry. 

PET Image Processing Laboratory
Numerous software applications have been developed in-house for performing image processing, analysis and viewing.  Applications are written in an X-windows based environment so that the user can run from any workstation or desktop computer with X-windows.  Portable programming techniques allow either the VMS cluster, or an individual's desktop computer to be the host processor.  Applications are available for: viewing images, kinetic modeling using a variety of techniques, automated region-of-interest (ROI) analysis, statistical analysis of image data using one or two groups, and creation and display of time-activity curves.  In addition to that, we utilize two different image registration packages (MIAMI FUSE and NeuroStat) for inter-subject, intra-subject, and multi-modality image registration to facilitate automated ROI analysis.

Single-Photon Emission Tomography for Animals
Two systems are available for animal imaging. Multiple rodent and large animal SPECT imaging is done using a Summit Nuclear Vision 1024R camera, interfaced with a Power Macintosh G3 for data collection and analysis. This camera is outfitted with a full set of collimators: low energy high resolution, low energy general purpose, low energy high sensitivity, medium energy high resolution, medium energy general purpose, and high energy general purpose. 

For dedicated SPECT imaging of small animals (rodents), a IN/US combined microSPECT/CT instrument was installed in January 2005.  This provides improved SPECT image resolution (approx 2 mm), with fully matched CT capabilities (for combining anatomical and molecular imaging).

Biodistribution Laboratory
The Biodistribution Laboratory of The Division of Nuclear Medicine screens and evaluates efficacy of new radiotracers or new applications of known tracers. It is fully outfitted with all necessary equipment, including balances, anesthesia machines, dissecting scopes, stereotactic equipment, gamma and beta counters, darkroom, computers, and a Fuji phosphorescence imager. All analytical equipment (balances, counters) are interfaced with the laboratory computer system for direct data abstraction and analysis. The biodistribution laboratory and personnel involved have performed more than a thousand animal biodistribution and imaging studies using beta-, gamma- and positron-emitting radionuclide labeled compounds.

Biochemistry and Cell Culture Laboratory
This space has four lab benches fully equipped for wet chemistry, including analytical balance, centrifuges, agitators, pH meter, fume hood and solvent storage cabinet.  Within this space is a separate 150 sq ft room, with HEPA filtered air, completely equipped for cell culture.  Equipment includes two 6 ft laminar flow hoods, two incubators (with CO2), refrigerator/freezer, microscope, water bath and liquid nitrogen tissue storage unit.  In adjacent laboratories, there are two -78 °C freezers, HPLC and darkroom facilities for radio-TLC and autoradiography. 

Shops
A fully equipped machine shop and electronic shop are contained within the laboratories for repair or fabrication of equipment.